To improve our understanding of pulmonary arteriovenous malformations in univentricular congenital heart disease, our objective was to identify the effects of hepatic vein and superior vena cava constituents on lung microvascular endothelial cells independent of blood flow. Paired blood samples were collected from the hepatic vein and superior vena cava in children 010 years old undergoing cardiac catheterization. Isolated serum was subsequently used for in vitro endothelial cell assays.
Angiogenic activity was assessed using tube formation and scratch migration. Endothelial cell survival was assessed using proliferation (BrdU incorporation, cell cycle analysis) and apoptosis (caspase 3/7 activity, Annexin-V labeling). Data were analyzed using Wilcoxon signed-rank test and repeated measures analysis. Upon incubating lung microvascular endothelial cells with 10% patient serum, hepatic vein
serum increases angiogenic activity (tube formation, P = 0.04, n = 24; migration, P< 0.001, n = 18), increases proliferation (BrdU, P < 0.001, n=32 S-phase, P= 0.04, n = 13), and decreases apoptosis (caspase 3/7, P < 0.001, n = 32; Annexin-V, P = 0.04, n = 12) compared to superior vena cava serum. Hepatic vein serum regulates lung microvascular endothelial cells by increasing angiogenesis and survival in vitro. Loss of hepatic vein serum signaling in the lung microvasculature may promote maladaptive lung microvascular remodeling and pulmonary arteriovenous malformations.
This document discusses various aspects of venovenous extracorporeal membrane oxygenation (VV ECMO) cannulation and management. It provides details on different cannulation strategies and their effects on recirculation. Specifically, it notes that femoro-atrial cannulation had significantly less flow requirement compared to atrio-femoral cannulation during VV ECMO. It also discusses techniques to minimize recirculation like using larger dual-lumen cannulae and ultrasound guidance for proper cannula positioning. Monitoring recirculation is important to optimize ECMO efficiency and outcomes.
The document discusses patient selection and management for pediatric and adult extracorporeal membrane oxygenation (ECMO). ECMO is considered for acute, life-threatening respiratory or cardiac conditions that are potentially reversible and unresponsive to conventional therapies. Younger age, fewer days on ventilation pre-ECMO, and better oxygenation predict survival. Venovenous ECMO is preferred over venoarterial when possible. Management involves lung rest through ventilator optimization, maintenance of adequate oxygenation and circulation, and treatment of complications like bleeding and infection during the ECMO run. Weaning and decannulation criteria include clinical and radiographic improvement allowing reduction and then discontinuation of ECMO support.
This document provides an overview of the evolution of concepts related to mechanical ventilation for acute respiratory distress syndrome (ARDS) from the 1940s to the present. Some key points discussed include:
1) Early work in the 1940s-1960s established that non-uniform lung expansion can cause excessive stress and harm capillaries, and that prone positioning may help improve lung homogeneity.
2) The 1980s-2000s saw a focus on tailoring ventilation to the "baby lung" concept and using lower tidal volumes, as well as recognizing ventilator-induced lung injury and the importance of lung recruitment and keeping the lung open.
3) Recent work has emphasized strain and stress concepts, the utility of
Extracorporeal membrane oxygenation (ECMO) is a temporary life support technique that uses a pump to circulate blood through an artificial lung back into the bloodstream. It can support heart and lung function for days to weeks while allowing the organs to rest. ECMO has been used since the 1940s and has evolved from supporting neonates to now supporting adults with severe cardiac or respiratory failure. It can be administered through venovenous (VV) or venoarterial (VA) cannulation depending on whether cardiac support is also needed.
The document discusses the use of extracorporeal membrane oxygenation (ECMO) as a treatment for acute respiratory distress syndrome (ARDS). It summarizes that ECMO can act as a bridge to allow the lungs to heal, but comes with risks of bleeding and other complications. While some early trials did not find benefit, more recent evidence from the CESAR trial in the UK showed reduced mortality for ARDS patients who received ECMO support at a specialized center, along with protocolized lung-protective ventilation. Further research is still needed to identify patient selection criteria and standardized protocols.
This case report describes a patient who developed a non-stump bronchopleural fistula (BPF) after a right lower lobectomy for lung cancer. On re-exploration, the bronchial stump was intact but the membranous portion of the bronchus intermedius was necrotic, causing a large fistula. The patient underwent a completion sleeve bilobectomy, removing the remaining middle lobe and performing a sleeve resection of the involved portion of the main bronchus. The upper lobe bronchus was re-anastomosed, and the patient recovered uneventfully with an intact bronchial anastomosis. This novel procedure successfully treated a rare case of non-stump BPF.
This document discusses various aspects of venovenous extracorporeal membrane oxygenation (VV ECMO) cannulation and management. It provides details on different cannulation strategies and their effects on recirculation. Specifically, it notes that femoro-atrial cannulation had significantly less flow requirement compared to atrio-femoral cannulation during VV ECMO. It also discusses techniques to minimize recirculation like using larger dual-lumen cannulae and ultrasound guidance for proper cannula positioning. Monitoring recirculation is important to optimize ECMO efficiency and outcomes.
The document discusses patient selection and management for pediatric and adult extracorporeal membrane oxygenation (ECMO). ECMO is considered for acute, life-threatening respiratory or cardiac conditions that are potentially reversible and unresponsive to conventional therapies. Younger age, fewer days on ventilation pre-ECMO, and better oxygenation predict survival. Venovenous ECMO is preferred over venoarterial when possible. Management involves lung rest through ventilator optimization, maintenance of adequate oxygenation and circulation, and treatment of complications like bleeding and infection during the ECMO run. Weaning and decannulation criteria include clinical and radiographic improvement allowing reduction and then discontinuation of ECMO support.
This document provides an overview of the evolution of concepts related to mechanical ventilation for acute respiratory distress syndrome (ARDS) from the 1940s to the present. Some key points discussed include:
1) Early work in the 1940s-1960s established that non-uniform lung expansion can cause excessive stress and harm capillaries, and that prone positioning may help improve lung homogeneity.
2) The 1980s-2000s saw a focus on tailoring ventilation to the "baby lung" concept and using lower tidal volumes, as well as recognizing ventilator-induced lung injury and the importance of lung recruitment and keeping the lung open.
3) Recent work has emphasized strain and stress concepts, the utility of
Extracorporeal membrane oxygenation (ECMO) is a temporary life support technique that uses a pump to circulate blood through an artificial lung back into the bloodstream. It can support heart and lung function for days to weeks while allowing the organs to rest. ECMO has been used since the 1940s and has evolved from supporting neonates to now supporting adults with severe cardiac or respiratory failure. It can be administered through venovenous (VV) or venoarterial (VA) cannulation depending on whether cardiac support is also needed.
The document discusses the use of extracorporeal membrane oxygenation (ECMO) as a treatment for acute respiratory distress syndrome (ARDS). It summarizes that ECMO can act as a bridge to allow the lungs to heal, but comes with risks of bleeding and other complications. While some early trials did not find benefit, more recent evidence from the CESAR trial in the UK showed reduced mortality for ARDS patients who received ECMO support at a specialized center, along with protocolized lung-protective ventilation. Further research is still needed to identify patient selection criteria and standardized protocols.
This case report describes a patient who developed a non-stump bronchopleural fistula (BPF) after a right lower lobectomy for lung cancer. On re-exploration, the bronchial stump was intact but the membranous portion of the bronchus intermedius was necrotic, causing a large fistula. The patient underwent a completion sleeve bilobectomy, removing the remaining middle lobe and performing a sleeve resection of the involved portion of the main bronchus. The upper lobe bronchus was re-anastomosed, and the patient recovered uneventfully with an intact bronchial anastomosis. This novel procedure successfully treated a rare case of non-stump BPF.
This document provides an overview of extracorporeal membrane oxygenation (ECMO) and its use in Hong Kong. It discusses the history and development of ECMO, how it works, common configurations including veno-venous and veno-arterial ECMO. It also outlines indications for ECMO use, important clinical studies that have supported its use, worldwide trends showing increased adoption of ECMO in recent years. Specifically for Hong Kong, it details the milestones in establishing ECMO programs across public hospitals to provide 24/7 ECMO services, statistics on ECMO use in Hong Kong, and the role of ECMO during public health crises including SARS and H1N1 influenza.
- ECMO is a form of extracorporeal life support that involves removing blood from the body, oxygenating it using an artificial lung, then returning it to circulate oxygenated blood through the body.
- It was first developed in the 1950s and saw its first successful use in 1971. It is now commonly used to support patients with severe cardiac and/or respiratory failure.
- There are two main types - venoarterial (VA) ECMO which supports cardiac function and venovenous (VV) ECMO which supports respiratory function. Indications, complications, and outcomes were discussed.
Hergen Buscher is an Intensivist from St Vincent's hospital in Sydney. He has extensive experience with ECMO, in both veno-venous and veno-arterial contexts. Listen to this talk he gave on the most recent developments in ECMO and where things are heading.
This talk was given live in September 2014 for an Intensive Care Network (ICN) NSW meeting.
Go to www.intensivecarenetwork.com for more.
This case report describes an 82-year-old male who developed intracardiac shunts following a redo aortic valve replacement surgery. Doppler echocardiography detected shunts from the left ventricle outflow tract across the membranous septum into the right atrium, right ventricle, and left atrium. The anatomical basis for this complication is the proximity and relationship of the thin membranous septum to the aortic root, tricuspid valve, and ventricular chambers. Aggressive debridement during valve surgery can cause injury and necrosis of the membranous septum, leading to fistula formation over time. While the shunts were initially small and asymptomatic, they could enlarge
1. Extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) are important life support therapies used in intensive care units.
2. ECMO uses an external circuit to oxygenate blood and remove carbon dioxide, functioning as a bridge to recovery, transplant, or decision. CRRT slowly removes waste and fluid from the blood of patients with kidney failure or injury.
3. The document discusses the principles, indications, techniques, and complications of ECMO and CRRT, highlighting their roles in supporting critically ill patients with cardiac, respiratory, or renal issues.
This document discusses the use of extracorporeal membrane oxygenation (ECMO) for managing severe hypoxia. It provides context on the definition of acute respiratory distress syndrome (ARDS) and outlines escalating interventions for ARDS of increasing severity, with ECMO as the highest level intervention. The history of ECMO is reviewed, noting early mixed results, but more recent randomized controlled trials and observational studies demonstrating improved survival with ECMO for severe ARDS. Indications for ECMO are discussed as refractory hypoxemia when other interventions like higher PEEP, prone positioning, and neuromuscular blockade have failed or are contraindicated. The future of ECMO is uncertain and more high-quality data from trials are
This document provides an overview of extracorporeal membrane oxygenation (ECMO) including its definition, history, components, configurations, physiology, indications, and complications. ECMO temporarily replaces or supports the cardiopulmonary system by extracting blood, oxygenating it through an artificial lung, then returning it to circulation. Key points include:
- ECMO was developed in the 1960s-70s and can support heart and/or lung function for weeks.
- The circuit includes cannulae, a pump, oxygenator, and controller. Configurations include venovenous (lung support) and venoarterial (heart and lung support).
- ECMO settings impact oxygen delivery and carbon dioxide
This document discusses anesthetic considerations for patients with advanced valvular heart disease undergoing noncardiac surgery. It begins by noting the increasing prevalence of valvular heart disease in the aging population. It then focuses on aortic stenosis, describing its epidemiology, causes, symptoms, pathophysiology and how the disease progresses. The key anesthetic considerations for patients with aortic stenosis are maintaining sinus rhythm, a slow heart rate, adequate preload and afterload to minimize the risk of myocardial ischemia due to the pathophysiology of the disease. Careful preoperative evaluation and perioperative management are important to optimize outcomes.
This document is the preface to a book titled "New Solutions for the Heart: An Update in Advanced Perioperative Protection". The preface discusses the motivation for creating the book, which was to provide a comprehensive summary of myocardial protection during cardiac surgery since the topic had not been covered in over 15 years. The editors, Bruno Podesser and David Chambers, recruited leading clinicians and scientists in the field of myocardial protection to contribute chapters on topics ranging from the history of cardioplegia to new technologies and approaches. The preface expresses the hope that the book will stimulate further research in myocardial protection to benefit cardiac surgery patients.
Extracoporeal Life Support presentation finalAshraf Banoub
1) Extracorporeal life support (ECLS) is a mechanical means of temporarily supporting heart and lung function during cardiopulmonary failure, allowing for organ recovery or replacement.
2) ECLS can be used for both cardiac and respiratory failure indications when mortality risks are high despite optimal conventional therapy.
3) The ECLS circuit involves removing blood from the body, oxygenating it using a membrane lung, and returning it to the body through vascular access via the veins and arteries. Proper blood flow and gas exchange parameters must be monitored and maintained.
This document summarizes a presentation on pulmonary embolism given in 2014. It discusses various treatment options for pulmonary embolism including heparin alone, thrombolytics, surgical embolectomy, and catheter directed therapy. It notes that guidelines support thrombolysis for massive PE but are vague on submassive PE. One study showed thrombolysis for submassive PE led to a decrease in mortality but increase in major bleeding. The presentation emphasizes treating high risk PE aggressively with a multidisciplinary team approach and considering thrombolysis or advanced procedures to reduce long term morbidity. It describes the creation of a PE advanced care team at the hospital.
Cabg is superior to pci in heart failure patients with multivessel disease co...drucsamal
PCI is a good alternative to CABG for revascularization in patients with heart failure and viable myocardium. Revascularization of viable myocardium may improve left ventricular function and remodeling, as well as quality of life and survival. While CABG is technically straightforward and evidence-based, PCI has less risk for patients with heart failure despite being technically challenging. More research is still needed comparing PCI to CABG and medical therapy alone for chronic heart failure. Treatment must be individualized based on patient characteristics and local clinical expertise.
This document summarizes a presentation by Dr. Eddy Fan on extracorporeal membrane oxygenation (ECMO) and lung protective ventilation strategies for acute respiratory distress syndrome (ARDS). The presentation discusses how ECMO can be used to facilitate lung rest and prevent ventilator-induced lung injury (VILI) in ARDS patients who cannot be safely ventilated with conventional lung protective strategies. It reviews evidence that ECMO combined with lower tidal volumes and plateau pressures may improve lung inflammation outcomes. However, optimal ventilation settings for ARDS patients on ECMO are still unknown. The presentation then describes the SOLVE ARDS study which aims to determine best practices for lung ventilation during ECMO through an international survey, systematic review,
This document discusses the use of extracorporeal membrane oxygenation (ECMO) for trauma patients. It provides an overview of ECMO, including configurations and goals of venovenous ECMO. Literature on outcomes of ECMO in trauma patients with acute respiratory failure is reviewed. Case studies are presented to critically evaluate the use of ECMO for distinct cohorts of trauma patients, including those with traumatic brain injury, massive chest trauma, and drowning.
This book is an edited collection on the topic of myocardial protection during cardiac surgery. It contains 34 chapters written by experts in the field covering the history and current strategies for protecting the heart during procedures. The editors are Tomas A. Salerno and Marco Ricci from the University of Miami.
This document provides an introduction to acute isovolemic hemodilution (AIH), a blood conservation technique. It describes the principles and advantages of AIH, such as reducing autologous blood transfusions and preserving clotting factors. Contraindications to AIH include shock, respiratory failure, and severe anemia. The procedure involves collecting blood prior to incision and replacing it with crystalloids or colloids to dilute the blood. The sequestered blood is returned after surgery. Formulas are provided to calculate blood volumes for hemodilution. The hospital is initiating an AIH protocol for certain surgeries to reduce transfusions.
Trali vs taco revised final may 26 2017 dr merayoJuan Merayo
This document discusses TRALI (transfusion-related acute lung injury) and TACO (transfusion-associated circulatory overload). It provides definitions and clinical characteristics of each condition. It notes that while TRALI has a low risk per RBC unit transfused of 1:10,000, TACO has a higher risk of 1:100. Both conditions can be fatal, with TRALI and TACO accounting for 38% and 24% respectively of reported transfusion fatalities from 2009-2015. The document reviews risk factors, diagnostic criteria, and mitigation strategies for each condition according to various regulatory and standards organizations.
ECMO (extracorporeal membrane oxygenation) is a technique that uses pumps and a artificial lung to support heart and lung function. It can be used to support failing organs while allowing time for recovery or as a bridge to transplant. The history of ECMO began in the 1950s with the development of cardiopulmonary bypass and its use has expanded to support both children and adults with heart and lung failure. While intensive, ECMO can save lives that would otherwise be lost to critical illness.
This study analyzed 45 observational studies including over 272,000 patients to determine the association between red blood cell transfusion and morbidity and mortality in high-risk hospitalized patients. The analysis found that in 42 of the 45 studies, the risks of red blood cell transfusion outweighed the benefits, with transfusion associated with increased risk of death, infections, multi-organ dysfunction syndrome, and acute respiratory distress syndrome. A meta-analysis found that transfusion was associated with 70% higher odds of death and 80% higher odds of developing an infectious complication. The study suggests current transfusion practices may need reevaluation given the risks appear to outweigh the benefits in most patients.
1) Pulmonary arterial hypertension (PAH) occurs in approximately 5% of adults with congenital heart disease (CHD) and accounts for 40-50% of PAH in children.
2) PAH is associated with increased mortality and morbidity in patients with CHD, with a 10-fold increase in mortality for those with Eisenmenger syndrome.
3) Targeted therapies have shown benefits for treating PAH in patients with CHD, though survival remains poor compared to other forms of PAH. Earlier diagnosis and treatment may help improve outcomes.
This document summarizes two studies on percutaneous left ventricular assist devices (LVADs) and coronary artery fistulas.
The first study investigated the ability of a percutaneous LVAD to deliver blood to the systemic circulation during cardiac arrest in pigs. The LVAD maintained blood flow and preferentially perfused vital organs like the brain. Intensified fluid loading further improved LVAD performance.
The second study evaluated the microvascular effects of ultrasound contrast (Definity) in hamsters with conditions like ischemia-reperfusion, diabetes, and sepsis. Inflammatory responses were higher in diabetes with ischemia and sepsis groups, independent of contrast use. Contrast did not alter hemodynamics or reology.
Primary hyperaldosteronism is characterized by an increase in
the adrenal production of aldosterone. It is critical for its treatment to determine whether it is caused by unilateral or bilateral overproduction of aldosterone. When imaging studies are ambiguous, adrenal venous sampling is the choice to confirm lateralization. It consists in dosing plasma aldosterone and cortisol in both adrenal veins simultaneously with the femoral vein, and establishing the aldosterone/cortisol ratio. On the affected side this ratio is at least 2 times higher than the femoral vein’s.
This document provides an overview of extracorporeal membrane oxygenation (ECMO) and its use in Hong Kong. It discusses the history and development of ECMO, how it works, common configurations including veno-venous and veno-arterial ECMO. It also outlines indications for ECMO use, important clinical studies that have supported its use, worldwide trends showing increased adoption of ECMO in recent years. Specifically for Hong Kong, it details the milestones in establishing ECMO programs across public hospitals to provide 24/7 ECMO services, statistics on ECMO use in Hong Kong, and the role of ECMO during public health crises including SARS and H1N1 influenza.
- ECMO is a form of extracorporeal life support that involves removing blood from the body, oxygenating it using an artificial lung, then returning it to circulate oxygenated blood through the body.
- It was first developed in the 1950s and saw its first successful use in 1971. It is now commonly used to support patients with severe cardiac and/or respiratory failure.
- There are two main types - venoarterial (VA) ECMO which supports cardiac function and venovenous (VV) ECMO which supports respiratory function. Indications, complications, and outcomes were discussed.
Hergen Buscher is an Intensivist from St Vincent's hospital in Sydney. He has extensive experience with ECMO, in both veno-venous and veno-arterial contexts. Listen to this talk he gave on the most recent developments in ECMO and where things are heading.
This talk was given live in September 2014 for an Intensive Care Network (ICN) NSW meeting.
Go to www.intensivecarenetwork.com for more.
This case report describes an 82-year-old male who developed intracardiac shunts following a redo aortic valve replacement surgery. Doppler echocardiography detected shunts from the left ventricle outflow tract across the membranous septum into the right atrium, right ventricle, and left atrium. The anatomical basis for this complication is the proximity and relationship of the thin membranous septum to the aortic root, tricuspid valve, and ventricular chambers. Aggressive debridement during valve surgery can cause injury and necrosis of the membranous septum, leading to fistula formation over time. While the shunts were initially small and asymptomatic, they could enlarge
1. Extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) are important life support therapies used in intensive care units.
2. ECMO uses an external circuit to oxygenate blood and remove carbon dioxide, functioning as a bridge to recovery, transplant, or decision. CRRT slowly removes waste and fluid from the blood of patients with kidney failure or injury.
3. The document discusses the principles, indications, techniques, and complications of ECMO and CRRT, highlighting their roles in supporting critically ill patients with cardiac, respiratory, or renal issues.
This document discusses the use of extracorporeal membrane oxygenation (ECMO) for managing severe hypoxia. It provides context on the definition of acute respiratory distress syndrome (ARDS) and outlines escalating interventions for ARDS of increasing severity, with ECMO as the highest level intervention. The history of ECMO is reviewed, noting early mixed results, but more recent randomized controlled trials and observational studies demonstrating improved survival with ECMO for severe ARDS. Indications for ECMO are discussed as refractory hypoxemia when other interventions like higher PEEP, prone positioning, and neuromuscular blockade have failed or are contraindicated. The future of ECMO is uncertain and more high-quality data from trials are
This document provides an overview of extracorporeal membrane oxygenation (ECMO) including its definition, history, components, configurations, physiology, indications, and complications. ECMO temporarily replaces or supports the cardiopulmonary system by extracting blood, oxygenating it through an artificial lung, then returning it to circulation. Key points include:
- ECMO was developed in the 1960s-70s and can support heart and/or lung function for weeks.
- The circuit includes cannulae, a pump, oxygenator, and controller. Configurations include venovenous (lung support) and venoarterial (heart and lung support).
- ECMO settings impact oxygen delivery and carbon dioxide
This document discusses anesthetic considerations for patients with advanced valvular heart disease undergoing noncardiac surgery. It begins by noting the increasing prevalence of valvular heart disease in the aging population. It then focuses on aortic stenosis, describing its epidemiology, causes, symptoms, pathophysiology and how the disease progresses. The key anesthetic considerations for patients with aortic stenosis are maintaining sinus rhythm, a slow heart rate, adequate preload and afterload to minimize the risk of myocardial ischemia due to the pathophysiology of the disease. Careful preoperative evaluation and perioperative management are important to optimize outcomes.
This document is the preface to a book titled "New Solutions for the Heart: An Update in Advanced Perioperative Protection". The preface discusses the motivation for creating the book, which was to provide a comprehensive summary of myocardial protection during cardiac surgery since the topic had not been covered in over 15 years. The editors, Bruno Podesser and David Chambers, recruited leading clinicians and scientists in the field of myocardial protection to contribute chapters on topics ranging from the history of cardioplegia to new technologies and approaches. The preface expresses the hope that the book will stimulate further research in myocardial protection to benefit cardiac surgery patients.
Extracoporeal Life Support presentation finalAshraf Banoub
1) Extracorporeal life support (ECLS) is a mechanical means of temporarily supporting heart and lung function during cardiopulmonary failure, allowing for organ recovery or replacement.
2) ECLS can be used for both cardiac and respiratory failure indications when mortality risks are high despite optimal conventional therapy.
3) The ECLS circuit involves removing blood from the body, oxygenating it using a membrane lung, and returning it to the body through vascular access via the veins and arteries. Proper blood flow and gas exchange parameters must be monitored and maintained.
This document summarizes a presentation on pulmonary embolism given in 2014. It discusses various treatment options for pulmonary embolism including heparin alone, thrombolytics, surgical embolectomy, and catheter directed therapy. It notes that guidelines support thrombolysis for massive PE but are vague on submassive PE. One study showed thrombolysis for submassive PE led to a decrease in mortality but increase in major bleeding. The presentation emphasizes treating high risk PE aggressively with a multidisciplinary team approach and considering thrombolysis or advanced procedures to reduce long term morbidity. It describes the creation of a PE advanced care team at the hospital.
Cabg is superior to pci in heart failure patients with multivessel disease co...drucsamal
PCI is a good alternative to CABG for revascularization in patients with heart failure and viable myocardium. Revascularization of viable myocardium may improve left ventricular function and remodeling, as well as quality of life and survival. While CABG is technically straightforward and evidence-based, PCI has less risk for patients with heart failure despite being technically challenging. More research is still needed comparing PCI to CABG and medical therapy alone for chronic heart failure. Treatment must be individualized based on patient characteristics and local clinical expertise.
This document summarizes a presentation by Dr. Eddy Fan on extracorporeal membrane oxygenation (ECMO) and lung protective ventilation strategies for acute respiratory distress syndrome (ARDS). The presentation discusses how ECMO can be used to facilitate lung rest and prevent ventilator-induced lung injury (VILI) in ARDS patients who cannot be safely ventilated with conventional lung protective strategies. It reviews evidence that ECMO combined with lower tidal volumes and plateau pressures may improve lung inflammation outcomes. However, optimal ventilation settings for ARDS patients on ECMO are still unknown. The presentation then describes the SOLVE ARDS study which aims to determine best practices for lung ventilation during ECMO through an international survey, systematic review,
This document discusses the use of extracorporeal membrane oxygenation (ECMO) for trauma patients. It provides an overview of ECMO, including configurations and goals of venovenous ECMO. Literature on outcomes of ECMO in trauma patients with acute respiratory failure is reviewed. Case studies are presented to critically evaluate the use of ECMO for distinct cohorts of trauma patients, including those with traumatic brain injury, massive chest trauma, and drowning.
This book is an edited collection on the topic of myocardial protection during cardiac surgery. It contains 34 chapters written by experts in the field covering the history and current strategies for protecting the heart during procedures. The editors are Tomas A. Salerno and Marco Ricci from the University of Miami.
This document provides an introduction to acute isovolemic hemodilution (AIH), a blood conservation technique. It describes the principles and advantages of AIH, such as reducing autologous blood transfusions and preserving clotting factors. Contraindications to AIH include shock, respiratory failure, and severe anemia. The procedure involves collecting blood prior to incision and replacing it with crystalloids or colloids to dilute the blood. The sequestered blood is returned after surgery. Formulas are provided to calculate blood volumes for hemodilution. The hospital is initiating an AIH protocol for certain surgeries to reduce transfusions.
Trali vs taco revised final may 26 2017 dr merayoJuan Merayo
This document discusses TRALI (transfusion-related acute lung injury) and TACO (transfusion-associated circulatory overload). It provides definitions and clinical characteristics of each condition. It notes that while TRALI has a low risk per RBC unit transfused of 1:10,000, TACO has a higher risk of 1:100. Both conditions can be fatal, with TRALI and TACO accounting for 38% and 24% respectively of reported transfusion fatalities from 2009-2015. The document reviews risk factors, diagnostic criteria, and mitigation strategies for each condition according to various regulatory and standards organizations.
ECMO (extracorporeal membrane oxygenation) is a technique that uses pumps and a artificial lung to support heart and lung function. It can be used to support failing organs while allowing time for recovery or as a bridge to transplant. The history of ECMO began in the 1950s with the development of cardiopulmonary bypass and its use has expanded to support both children and adults with heart and lung failure. While intensive, ECMO can save lives that would otherwise be lost to critical illness.
This study analyzed 45 observational studies including over 272,000 patients to determine the association between red blood cell transfusion and morbidity and mortality in high-risk hospitalized patients. The analysis found that in 42 of the 45 studies, the risks of red blood cell transfusion outweighed the benefits, with transfusion associated with increased risk of death, infections, multi-organ dysfunction syndrome, and acute respiratory distress syndrome. A meta-analysis found that transfusion was associated with 70% higher odds of death and 80% higher odds of developing an infectious complication. The study suggests current transfusion practices may need reevaluation given the risks appear to outweigh the benefits in most patients.
1) Pulmonary arterial hypertension (PAH) occurs in approximately 5% of adults with congenital heart disease (CHD) and accounts for 40-50% of PAH in children.
2) PAH is associated with increased mortality and morbidity in patients with CHD, with a 10-fold increase in mortality for those with Eisenmenger syndrome.
3) Targeted therapies have shown benefits for treating PAH in patients with CHD, though survival remains poor compared to other forms of PAH. Earlier diagnosis and treatment may help improve outcomes.
Similar to Hepatic Vein Blood Increases Lung Microvascular Angiogenesis and Endothelial Cell Survival—Toward an Understanding of Univentricular Circulation
This document summarizes two studies on percutaneous left ventricular assist devices (LVADs) and coronary artery fistulas.
The first study investigated the ability of a percutaneous LVAD to deliver blood to the systemic circulation during cardiac arrest in pigs. The LVAD maintained blood flow and preferentially perfused vital organs like the brain. Intensified fluid loading further improved LVAD performance.
The second study evaluated the microvascular effects of ultrasound contrast (Definity) in hamsters with conditions like ischemia-reperfusion, diabetes, and sepsis. Inflammatory responses were higher in diabetes with ischemia and sepsis groups, independent of contrast use. Contrast did not alter hemodynamics or reology.
Primary hyperaldosteronism is characterized by an increase in
the adrenal production of aldosterone. It is critical for its treatment to determine whether it is caused by unilateral or bilateral overproduction of aldosterone. When imaging studies are ambiguous, adrenal venous sampling is the choice to confirm lateralization. It consists in dosing plasma aldosterone and cortisol in both adrenal veins simultaneously with the femoral vein, and establishing the aldosterone/cortisol ratio. On the affected side this ratio is at least 2 times higher than the femoral vein’s.
MDCT Evaluation of Varices in Portal HypertensionVishwanath R S
MDCT is useful for identifying portosystemic collateral vessels in patients with portal hypertension. It can accurately demonstrate the majority of collateral channels. Dynamic CT with contrast allows visualization of varices in the esophagus, stomach, rectum, and other locations. Precise mapping of collateral vessels is important before surgical or interventional procedures to avoid blood loss. MDCT plays an invaluable role in managing portal hypertension.
Researchers in Sweden successfully recellularized decellularized human blood vessels with autologous whole peripheral blood. They then used the recellularized vessels for bypass procedures in two patients with portal vein thrombosis. The work demonstrates that personalized blood vessels can be generated using a simple blood sample from the patient. The researchers were able to repopulate decellularized allogeneic vascular scaffolds with peripheral whole blood in vitro in a bioreactor. Circulating cells contributed to repopulation of the grafts. Scanning electron micrographs showed cells with a flat morphology consistent with endothelial cells on the luminal surface.
Acute Myelopathy- Vascular and Infectious Diseases.pdfssuser98b21a
1. Acute myelopathy can be caused by vascular or infectious diseases of the spinal cord. Vascular causes include spinal cord infarction from occlusion of the anterior or posterior spinal arteries, as well as vascular malformations like arteriovenous malformations.
2. Infectious causes include cord compression, intrinsic cord injury, or cord ischemia from conditions like epidural abscess. Rapid imaging can identify the pathological process and guide antimicrobial treatment and other medical or surgical management.
3. Management of acute spinal cord infarction focuses on intravascular volume resuscitation, blood pressure support, and prevention of medical complications. Outcomes are limited due to lack of effective treatments for established infarction.
Partial Exchange Transfussion In Polycythemia Secondary To Complex Cyanotic H...AR Muhamad Na'im
This patient is a 12-year-old girl with pulmonary atresia and ventricular septal defect who presents with symptoms of hyperviscosity due to polycythemia. She has undergone partial exchange transfusions every 4 months to manage her polycythemia. Examination revealed central cyanosis, clubbing, and a heart murmur. Laboratory tests showed hemoglobin of 21.9 g/dL and hematocrit of 68.7%. She underwent a successful partial exchange transfusion of 400 mL to reduce her hematocrit and symptoms. Partial exchange transfusion is an established treatment for polycythemia in cyanotic heart disease patients to reduce viscosity and improve oxygen delivery.
Abnormal Ductus Venosus Flow With Increased Nuchal TranslucencyTony Terrones
This study evaluated ductus venosus flow velocities in fetuses with increased nuchal translucency (NT) and examined whether flow alterations were related to specific types of cardiac defects. The study included 72 fetuses with normal NT and 137 fetuses with increased NT. Abnormal ductus venosus flow, including higher pulsatility index for veins and lower late diastolic velocity, was seen in fetuses with increased NT, particularly those with cardiac defects. However, ductus venosus flow did not differ between types of cardiac defects. This suggests that altered ductus venosus flow in fetuses with increased NT is not explained by cardiac failure from a specific cardiac anatomy.
1. The document discusses Chronic Cerebrospinal Venous Insufficiency (CCSVI), a condition linked to multiple sclerosis (MS) where veins draining the brain and spinal cord are narrowed or blocked.
2. It provides details on diagnosing and treating CCSVI using procedures like Doppler ultrasound, MRI, venography, and venous angioplasty to widen blocked veins.
3. While the relationship between CCSVI and MS is still being studied, the document reports that over 600 MS patients treated for CCSVI experienced reduced fatigue, improved quality of life, psychological state, and physical condition based on evaluation scales.
Vascular diseases are increasing health problems affecting > 25 million individuals in westernized societies. Such patients could benefit from transplantation of tissue-engineered vascular grafts using autologous cells. One challenge that has limited this development is the need for cell isolation, and risks associated with ex vivo expanded stem cells. Here we demonstrate a novel approach to generate transplantable vascular grafts using decellularized allogeneic vascular scaffolds, repopulated with peripheral whole blood (PWB) in vitro in a bioreactor. Circulating, VEGFR-2 +/CD45 + and a smaller fraction of VEGFR-2 +/CD14 + cells contributed to repopulation of the graft. SEM micrographs showed flat cells on the luminal surface of the grafts consistent with endothelial cells. For clinical validation, two autologous PWB tissue-engineered vein conduits were prepared and successfully used for by-pass procedures in two pediatric patients. These results provide a proof of principle for the generation of transplantable vascular grafts using a simple autologous blood sample, making it clinically feasible globally.
Vascular diseases are increasing health problems affecting > 25 million individuals in westernized societies. Such patients could benefit from transplantation of tissue-engineered vascular grafts using autologous cells. One challenge that has limited this development is the need for cell isolation, and risks associated with ex vivo expanded stem cells. Here we demonstrate a novel approach to generate transplantable vascular grafts using decellularized allogeneic vascular scaffolds, repopulated with peripheral whole blood (PWB) in vitro in a bioreactor. Circulating, VEGFR-2 +/CD45 + and a smaller fraction of VEGFR-2 +/CD14 + cells contributed to repopulation of the graft. SEM micrographs showed flat cells on the luminal surface of the grafts consistent with endothelial cells. For clinical validation, two autologous PWB tissue-engineered vein conduits were prepared and successfully used for by-pass procedures in two pediatric patients. These results provide a proof of principle for the generation of transplantable vascular grafts using a simple autologous blood sample, making it clinically feasible globally.
Vein of Galen malformations are rare congenital vascular anomalies that develop between weeks 6-11 of fetal development. They present as an aneurysmally dilated midline deep venous structure fed by abnormal arteriovenous communications. In neonates, they can cause high-output cardiac failure. Older children and adults may present with hydrocephalus, neurological deficits, or seizures. Diagnosis is made through imaging like CT, MRI, and angiography. Treatment involves endovascular embolization of the arteriovenous shunts to reduce cardiac overload and improve neurological outcomes. With advances in interventional neuroradiology, vein of Galen malformations can now be successfully treated with low complication rates.
This review article discusses microvascular and macrovascular disease in systemic hypertension. It summarizes that:
1) Cardiac imaging plays a crucial role in risk stratifying hypertensive patients and identifying management strategies by properly diagnosing microvascular and coronary artery disease.
2) The nitric oxide synthase (eNOS) G298 gene allele may be a marker for microvascular angina in hypertensive patients, as studies have found it to be more prevalent in hypertensive patients with chest pain and reversible myocardial defects but normal coronary arteries.
3) Both structural changes like capillary rarefaction and functional changes like endothelial dysfunction can cause microvascular dysfunction and angina in hypertensive individuals in the absence of
This study examined the relationship between volume overhydration and endothelial dysfunction in 81 stable patients on continuous ambulatory peritoneal dialysis. Volume status was assessed by normalized extracellular water and endothelial function was estimated by flow-mediated dilation of the brachial artery. There was an independent correlation between the index of volume status (normalized extracellular water) and endothelial function (flow-mediated dilation), with higher normalized extracellular water related to worse endothelial function. Multiple regression analysis identified calcium-phosphate product, normalized extracellular water, and dialysis vintage as independent determinants of endothelial function. The results suggest that volume overhydration may lead to increased cardiovascular risk in dialysis patients through its effects on endothelial dysfunction.
- This study evaluated clinical outcomes of peritoneal dialysis (PD) patients depending on the absence or presence of liver cirrhosis (LC), using a propensity score matching method.
- They found that early technical complications, peritonitis, long-term PD use, and patient survival were not higher in patients with LC compared to those without. However, transition to hemodialysis occurred slightly faster in LC patients.
- The study suggests that PD can be recommended for end-stage renal disease patients with LC without additional risks, and may have advantages over hemodialysis for these patients.
This randomized trial compared outcomes of 539 European patients with acute ischemic stroke treated with either endovascular treatment (EVT) alone or intravenous alteplase followed by EVT. The trial found no significant difference in functional outcomes at 90 days between the two treatment groups as measured by the modified Rankin scale. Rates of death and symptomatic intracerebral hemorrhage were also similar between groups. Therefore, the trial demonstrated that EVT alone was neither superior nor non-inferior to intravenous alteplase followed by EVT for acute ischemic stroke patients in Europe.
IMAGES OF A COMPLEX CASE OF MULTIPLE ANEURYSMAL DISEASE IN A 58 YEAR OLD MAN
IMMAGINI DI UN CASO COMPLESSO DI MALATTIA POLINEURISMATICA
(Chirurgia Vascolare-ULSS 15 Alta Padovana)
(Vascular Surgery -ULSS 15 Alta Padovana)
Intramyocardial Angiogenic Cell Precursors in Non-Ischemic Dilated Cardiomyop...lifextechnologies
This study investigated injecting angiogenic cell precursors directly into the left ventricle of 35 patients with nonischemic dilated cardiomyopathy. 17 similar patients receiving only medical treatment served as controls. After injection, 71.4% of patients in the cell group showed improved left ventricular ejection fraction and NYHA functional class. Quality of life also improved. The control group showed no significant improvements. The study concluded intramyocardial injection of angiogenic cells is effective for treating nonischemic dilated cardiomyopathy.
This study reviewed 86 patients who underwent pericardiectomy for chronic constrictive pericarditis (CCP) at a single center from 2010-2014. Preoperatively, most patients were in NYHA class II or III. Tuberculosis was the cause of CCP in 32.6% of patients. The overall mortality rate was 2.3%. Postoperatively, 90.6% of surviving patients were in NYHA class I or II. The results showed pericardiectomy to be an effective treatment for CCP, with tuberculosis remaining a common cause in India.
Introduction: There is growing evidence that Obstructive Sleep Apnea (OSA) is a risk factor for Pulmonary Embolism (PE). This
association represents a major public health burden.Aims and Objectives: To investigate Computed Tomography Obstruction Index (CTOI) and the Right Ventricular (RV) to Left Ventricular (LV) diameter ratio with OSA severity. Materials and Methods: 46 Patients with (PE) were evaluated for OSA. Pulmonary Artery Obstruction Index (PAOI) and RV/ LV diameter ratio was measured by pulmonary angiography. Pulmonary Embolism Severity Index (PESI) was determined. Epworth Sleepiness Scale (ESS) and Polysomnography (PSG) was performed for all patients. Based on the PAOI, patients divided into (< 15%, 15-50%, > 50%).
Invasive hemodynamic monitoring using a pulmonary artery catheter can help guide treatment for complex patients by providing detailed cardiac information. While use of these catheters is declining somewhat, the data they provide on issues like cardiogenic shock and pulmonary pressures can still be useful for diagnosis and management. For a complex patient, this information could be used to individualize a treatment plan involving medications, devices, or other therapies. However, there are also risks to consider from potential complications of catheter insertion or use.
Similar to Hepatic Vein Blood Increases Lung Microvascular Angiogenesis and Endothelial Cell Survival—Toward an Understanding of Univentricular Circulation (20)
The current study investigated the immunomodulatory
potential of ethyl acetate soluble supernatant of
Lactobacillus casei (LC-EAS) in vitro. The effect of
LC-EAS on nitric oxide release was analyzed in RAW
264.7 cells, wherein, an inhibition in nitric oxide production
through suppression of inducible nitric oxide synthase
mRNA expression was observed. Evaluation of LC-EAS
on LPS-induced peripheral blood mononuclear cells
showed a down-regulation in TNF-a and IL-6 genes and an
upregulation of IL-10. An inhibition in the protein
expression of NF-kB, ERK1/2 and STAT3 phosphorylation
confirms the immunomodulatory potential of LC-EAS. The
effect of LC-EAS on in vitro intestinal epithelial cells was
investigated using HT-29 human colon adenocarcinoma
cancer cells. LC-EAS exhibited an inhibition of NF-jB and
ERK1/2 phosphorylation, whereas STAT3 phosphorylation
was unregulated. To evaluate the downstream target of
STAT3 upregulation, expression of the intestinal trefoil
factor TFF3 which is a NF-jB regulator and STAT3
downstream target was studied. LC-EAS was observed to
elevate TFF3 mRNA expression. Overall the study shows
that the anti-inflammatory potential of LC-EAS is through
inhibition of NF-kB in different cell types.
Tetrahydrobiopterin in antenatal brain hypoxia-ischemia-induced motor impairm...KarthikeyanThirugnan3
This document discusses tetrahydrobiopterin (BH4) and its role in antenatal brain hypoxia-ischemia, a significant cause of cerebral palsy and motor impairments in children. BH4 is an important enzyme cofactor necessary for neurotransmitter production and brain redox homeostasis. Experimental hypoxia-ischemia in immature brains causes a decline in BH4 availability that coincides with loss of brain function, suggesting BH4 deficiency contributes to neuronal dysfunction and motor impairments. The document reviews different genetic deficiencies affecting the BH4 pathway and their associated neurological symptoms, as well as evidence that oxidative stress can also impact BH4 levels and exacerbate certain deficiencies.
Cystathione -synthase regulates HIF-1 stability through persulfidation of PHD2KarthikeyanThirugnan3
The stringent expression of the hypoxia inducible factor-1 (HIF-1) is critical to a variety of pathophysiological
conditions. We reveal that, in normoxia, enzymatic action of cystathionine -synthase (CBS) produces H2S, which
persulfidates prolyl hydroxylase 2 (PHD2) at residues Cys21 and Cys33 (zinc finger motif), augmenting prolyl hydroxylase
activity. Depleting endogenous H2S either by hypoxia or by inhibiting CBS via chemical or genetic means
reduces persulfidation of PHD2 and inhibits activity, preventing hydroxylation of HIF-1, resulting in stabilization.
Our in vitro findings are further supported by the depletion of CBS in the zebrafish model that exhibits axis defects
and abnormal intersegmental vessels. Exogenous H2S supplementation rescues both in vitro and in vivo phenotypes.
We have identified the persulfidated residues and defined their functional significance in regulating the
activity of PHD2 via point mutations. Thus, the CBS/H2S/PHD2 axis may provide therapeutic opportunities for pathologies
associated with HIF-1 dysregulation in chronic diseases.
Hypertonia is pathognomonic of cerebral palsy (CP), often caused by brain injury before birth. To understand the
early driving events of hypertonia, we utilized magnetic resonance imaging (MRI) assessment of early critical
brain injury in rabbit fetuses (79% term) that will predict hypertonia after birth following antenatal hypoxiaischemia.
We examined if individual variations in the tetrahydrobiopterin cofactor in the parts of the brain
controlling motor function could indicate a role in specific damage to motor regions and disruption of circuit
integration as an underlying mechanism for acquiring motor disorders, which has not been considered before.
The rabbit model mimicked acute placental insufficiency and used uterine ischemia at a premature gestation.
MRI during the time of hypoxia-ischemia was used to differentiate which individual fetal brains would become
hypertonic. Four brain regions collected immediately after hypoxia-ischemia or 48 h later were analyzed in a
blinded fashion. Age-matched sham-operated animals were used as controls. Changes in the reactive nitrogen
species and gene expression of the tetrahydrobiopterin biosynthetic enzymes in brain regions were also studied.
We found that a combination of low tetrahydrobiopterin content in the cortex, basal ganglia, cerebellum, and
thalamus brain regions, but not a unique low threshold of tetrahydrobiopterin, contributed etiologically to
hypertonia. The biggest contribution was from the thalamus. Evidence for increased reactive nitrogen species
was found in the cortex. By 48 h, tetrahydrobiopterin and gene expression levels in the different parts of the
brain were not different between MRI stratified hypertonia and non-hypertonia groups. Sepiapterin treatment
given to pregnant dams immediately after hypoxia-ischemia ameliorated hypertonia and death. We conclude
that a developmental tetrahydrobiopterin variation is necessary with fetal hypoxia-ischemia and is critical for
disrupting normal motor circuits that develop into hypertonia. The possible mechanistic pathway involves reactive
nitrogen species.
Cardiac inflammation plays a major role during myocardial infarction, reduction of inflammation decreases the severity of disease progression. SNRK is a AMPK family member protein which is highly involved in decreasing the inflammation in heart and protects cardiac function.
Unlocking the mysteries of reproduction: Exploring fecundity and gonadosomati...AbdullaAlAsif1
The pygmy halfbeak Dermogenys colletei, is known for its viviparous nature, this presents an intriguing case of relatively low fecundity, raising questions about potential compensatory reproductive strategies employed by this species. Our study delves into the examination of fecundity and the Gonadosomatic Index (GSI) in the Pygmy Halfbeak, D. colletei (Meisner, 2001), an intriguing viviparous fish indigenous to Sarawak, Borneo. We hypothesize that the Pygmy halfbeak, D. colletei, may exhibit unique reproductive adaptations to offset its low fecundity, thus enhancing its survival and fitness. To address this, we conducted a comprehensive study utilizing 28 mature female specimens of D. colletei, carefully measuring fecundity and GSI to shed light on the reproductive adaptations of this species. Our findings reveal that D. colletei indeed exhibits low fecundity, with a mean of 16.76 ± 2.01, and a mean GSI of 12.83 ± 1.27, providing crucial insights into the reproductive mechanisms at play in this species. These results underscore the existence of unique reproductive strategies in D. colletei, enabling its adaptation and persistence in Borneo's diverse aquatic ecosystems, and call for further ecological research to elucidate these mechanisms. This study lends to a better understanding of viviparous fish in Borneo and contributes to the broader field of aquatic ecology, enhancing our knowledge of species adaptations to unique ecological challenges.
The debris of the ‘last major merger’ is dynamically youngSérgio Sacani
The Milky Way’s (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the
‘last major merger.’ Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor
collided with the MW proto-disc 8–11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the
MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space,
because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia
DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations
at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based
on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1–2 Gyr ago.
We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative
measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data
1–2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the ‘last major merger’
did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within
the last few Gyr, consistent with the body of work surrounding the VRM.
Current Ms word generated power point presentation covers major details about the micronuclei test. It's significance and assays to conduct it. It is used to detect the micronuclei formation inside the cells of nearly every multicellular organism. It's formation takes place during chromosomal sepration at metaphase.
Phenomics assisted breeding in crop improvementIshaGoswami9
As the population is increasing and will reach about 9 billion upto 2050. Also due to climate change, it is difficult to meet the food requirement of such a large population. Facing the challenges presented by resource shortages, climate
change, and increasing global population, crop yield and quality need to be improved in a sustainable way over the coming decades. Genetic improvement by breeding is the best way to increase crop productivity. With the rapid progression of functional
genomics, an increasing number of crop genomes have been sequenced and dozens of genes influencing key agronomic traits have been identified. However, current genome sequence information has not been adequately exploited for understanding
the complex characteristics of multiple gene, owing to a lack of crop phenotypic data. Efficient, automatic, and accurate technologies and platforms that can capture phenotypic data that can
be linked to genomics information for crop improvement at all growth stages have become as important as genotyping. Thus,
high-throughput phenotyping has become the major bottleneck restricting crop breeding. Plant phenomics has been defined as the high-throughput, accurate acquisition and analysis of multi-dimensional phenotypes
during crop growing stages at the organism level, including the cell, tissue, organ, individual plant, plot, and field levels. With the rapid development of novel sensors, imaging technology,
and analysis methods, numerous infrastructure platforms have been developed for phenotyping.
The binding of cosmological structures by massless topological defectsSérgio Sacani
Assuming spherical symmetry and weak field, it is shown that if one solves the Poisson equation or the Einstein field
equations sourced by a topological defect, i.e. a singularity of a very specific form, the result is a localized gravitational
field capable of driving flat rotation (i.e. Keplerian circular orbits at a constant speed for all radii) of test masses on a thin
spherical shell without any underlying mass. Moreover, a large-scale structure which exploits this solution by assembling
concentrically a number of such topological defects can establish a flat stellar or galactic rotation curve, and can also deflect
light in the same manner as an equipotential (isothermal) sphere. Thus, the need for dark matter or modified gravity theory is
mitigated, at least in part.
The use of Nauplii and metanauplii artemia in aquaculture (brine shrimp).pptxMAGOTI ERNEST
Although Artemia has been known to man for centuries, its use as a food for the culture of larval organisms apparently began only in the 1930s, when several investigators found that it made an excellent food for newly hatched fish larvae (Litvinenko et al., 2023). As aquaculture developed in the 1960s and ‘70s, the use of Artemia also became more widespread, due both to its convenience and to its nutritional value for larval organisms (Arenas-Pardo et al., 2024). The fact that Artemia dormant cysts can be stored for long periods in cans, and then used as an off-the-shelf food requiring only 24 h of incubation makes them the most convenient, least labor-intensive, live food available for aquaculture (Sorgeloos & Roubach, 2021). The nutritional value of Artemia, especially for marine organisms, is not constant, but varies both geographically and temporally. During the last decade, however, both the causes of Artemia nutritional variability and methods to improve poorquality Artemia have been identified (Loufi et al., 2024).
Brine shrimp (Artemia spp.) are used in marine aquaculture worldwide. Annually, more than 2,000 metric tons of dry cysts are used for cultivation of fish, crustacean, and shellfish larva. Brine shrimp are important to aquaculture because newly hatched brine shrimp nauplii (larvae) provide a food source for many fish fry (Mozanzadeh et al., 2021). Culture and harvesting of brine shrimp eggs represents another aspect of the aquaculture industry. Nauplii and metanauplii of Artemia, commonly known as brine shrimp, play a crucial role in aquaculture due to their nutritional value and suitability as live feed for many aquatic species, particularly in larval stages (Sorgeloos & Roubach, 2021).
Authoring a personal GPT for your research and practice: How we created the Q...Leonel Morgado
Thematic analysis in qualitative research is a time-consuming and systematic task, typically done using teams. Team members must ground their activities on common understandings of the major concepts underlying the thematic analysis, and define criteria for its development. However, conceptual misunderstandings, equivocations, and lack of adherence to criteria are challenges to the quality and speed of this process. Given the distributed and uncertain nature of this process, we wondered if the tasks in thematic analysis could be supported by readily available artificial intelligence chatbots. Our early efforts point to potential benefits: not just saving time in the coding process but better adherence to criteria and grounding, by increasing triangulation between humans and artificial intelligence. This tutorial will provide a description and demonstration of the process we followed, as two academic researchers, to develop a custom ChatGPT to assist with qualitative coding in the thematic data analysis process of immersive learning accounts in a survey of the academic literature: QUAL-E Immersive Learning Thematic Analysis Helper. In the hands-on time, participants will try out QUAL-E and develop their ideas for their own qualitative coding ChatGPT. Participants that have the paid ChatGPT Plus subscription can create a draft of their assistants. The organizers will provide course materials and slide deck that participants will be able to utilize to continue development of their custom GPT. The paid subscription to ChatGPT Plus is not required to participate in this workshop, just for trying out personal GPTs during it.
Remote Sensing and Computational, Evolutionary, Supercomputing, and Intellige...University of Maribor
Slides from talk:
Aleš Zamuda: Remote Sensing and Computational, Evolutionary, Supercomputing, and Intelligent Systems.
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Inter-Society Networking Panel GRSS/MTT-S/CIS Panel Session: Promoting Connection and Cooperation
https://www.etran.rs/2024/en/home-english/
The technology uses reclaimed CO₂ as the dyeing medium in a closed loop process. When pressurized, CO₂ becomes supercritical (SC-CO₂). In this state CO₂ has a very high solvent power, allowing the dye to dissolve easily.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
Describing and Interpreting an Immersive Learning Case with the Immersion Cub...Leonel Morgado
Current descriptions of immersive learning cases are often difficult or impossible to compare. This is due to a myriad of different options on what details to include, which aspects are relevant, and on the descriptive approaches employed. Also, these aspects often combine very specific details with more general guidelines or indicate intents and rationales without clarifying their implementation. In this paper we provide a method to describe immersive learning cases that is structured to enable comparisons, yet flexible enough to allow researchers and practitioners to decide which aspects to include. This method leverages a taxonomy that classifies educational aspects at three levels (uses, practices, and strategies) and then utilizes two frameworks, the Immersive Learning Brain and the Immersion Cube, to enable a structured description and interpretation of immersive learning cases. The method is then demonstrated on a published immersive learning case on training for wind turbine maintenance using virtual reality. Applying the method results in a structured artifact, the Immersive Learning Case Sheet, that tags the case with its proximal uses, practices, and strategies, and refines the free text case description to ensure that matching details are included. This contribution is thus a case description method in support of future comparative research of immersive learning cases. We then discuss how the resulting description and interpretation can be leveraged to change immersion learning cases, by enriching them (considering low-effort changes or additions) or innovating (exploring more challenging avenues of transformation). The method holds significant promise to support better-grounded research in immersive learning.
2. Keywords: Congenital heart disease, Pulmonary arteriovenous malformations,
Lung microvasculature, Pediatric
INTRODUCTION
Children born with functionally univentricular congenital heart
disease (CHD) are increasingly surviving to adulthood.1À3
Despite
improved survival, children with univentricular CHD are at risk
for multiple complications. A common complication is the forma-
tion of pulmonary arteriovenous malformations (PAVMs).4,5
PAVMs are abnormal vascular connections between arteries and
veins in the lungs. Because PAVMs bypass the capillary bed,
PAVMs cause hypoxia and can decrease quality of life. PAVMs
develop as an unintended complication in 60À100% of patients
who undergo staged surgical palliation for univentricular CHD.6,7
Despite the regular occurrence of CHD-associated PAVMs, little is
known about them, and there are no effective medical therapies
to treat CHD-associated PAVMs.8À10
Clinical observations indicate that an unidentified factor in
hepatic vein (HV) blood, called hepatic factor, is protective against
developing PAVMs and can resolve existing PAVMs.11,12
Hepatic
factor is excluded from pulmonary blood flow after surgical pallia-
tion with a superior cavopulmonary connection (SCPC), also
known as Glenn palliation. In SCPC circulation, pulmonary blood
flow is nonpulsatile and provided exclusively from superior vena
cava (SVC) blood. PAVMs develop after SCPC palliation. After
subsequent palliation with a total cavopulmonary connection
(TCPC), also known as Fontan palliation, pulmonary blood flow
remains nonpulsatile, but HV blood is re-directed to the pulmo-
nary vasculature. PAVMs usually resolve over weeks to months
after TCPC with re-incorporation of HV blood despite blood flow
remaining nonpulsatile.
PAVM formation is a dynamic process of vascular remodel-
ing. Animal models of SCPC palliation indicate that PAVMs
may develop due to dysregulated angiogenesis, proliferation,
and oxidative stress.13À15
The specific contributions of HV and
SVC blood to regulate these fundamental cellular processes in
the lung microvasculature are not well understood. Addition-
ally, it remains unknown whether the cellular and molecular
changes in these animal models of PAVMs are due to HV and
SVC constituents or due to changes in blood flow from pulsa-
tile to nonpulsatile. We hypothesized that HV and SVC constit-
uents would differentially impact lung microvascular
endothelial cells (ECs). In this study, we used blood samples
from pediatric-age patients to investigate the effects of HV and
SVC blood on lung microvascular ECs independent of flow.
METHODS
Patient Selection and Blood Sample Collection
Blood samples were collected from children 0 to 10 years old
undergoing cardiac catheterization at Children’s Hospital of
Wisconsin after obtaining parental written informed consent.
Using fluoroscopic guidance, blood samples were specifically
collected from 2 anatomic locations: (#1) the SVC and (#2)
immediately cephalad to the HV insertion into the inferior
vena cava. Site #2 will be referred to as HV. The volume of
sample drawn was based on patient size. This study was
approved by the institutional review board.
After blood collection, samples were allowed to coagulate at
room temperature for 30 minutes and centrifuged at 2000£ g
for 15 minutes at 4°C. Serum was then aspirated, aliquoted,
and stored at À80°C.
Data regarding patient diagnosis and clinical variables were
obtained from the medical record. PAVMs were diagnosed
using echocardiographic bubble studies during cardiac cathe-
terization. PAVMs were suspected in patients with univentricu-
lar circulation without a bubble study if they had hypoxia
(oxygen saturation [SpO2] <80% for SCPC circulation or
<90% for TCPC circulation) without significant veno-venous
collaterals, abnormal angiographic appearance of the pulmo-
nary vasculature, or pulmonary vein desaturation (SvO2
<95%).
Cell Culture
Primary human pulmonary microvascular ECs (HPMECs)
isolated from the lung of a single donor were purchased and
used for all experiments (Promocell, #C-12281). Mycoplasma-
free cells were grown and maintained in Endothelial cell
growth medium MV (Promocell, #C-22020) and studied at
passage 4À6.
Angiogenesis: Tube Formation
One day prior to tube formation assay, reduced growth fac-
tor Matrigel (VWR, #47743-718) was thawed overnight at 4°C
and contact inhibited HPMECs were serum-starved overnight
in 0.5% fetal bovine serum (FBS). Undiluted Matrigel was
added (65 mL) to each well of a 96-well plate and allowed to
solidify at 37°C for 1 hour. HPMECs were then trypsinized,
counted, and 1 £ 104
cells/well were added after mixing cells
with 10% patient serum (triplicate). HPMECs were then incu-
bated at 37°C for 4 hours. Tube formation was visualized using
Keyence BZ-X700 bright-field/fluorescent microscope (Japan).
Images were empirically obtained from the center of each well
and analyzed with ImageJ using the “Angiogenesis Analyzer”
function to quantify number of nodes, number of tubes, and
tube length. The average of each sample (triplicate) was used
for statistical analysis and is reported relative to control
(HPMEC treated with complete growth medium).
Angiogenesis: Scratch Migration
HPMECs were grown to confluence in a 24-well plate and
then serum starved overnight in 0.5% FBS. The confluent
monolayer was scratched with a sterile P200 pipette tip to cre-
ate a zone free of HPMECs. The media was then gently aspi-
rated and replaced with 10% patient serum in triplicate.
CONGENITAL À Original Submission
2 Seminars in Thoracic and Cardiovascular Surgery Volume 00, Number 00
3. Images from each well were obtained using Keyence BZ-X700
bright-field/fluorescent microscope immediately after replacing
media (time (t) = 0 hours) and after 8-hour incubation at 37°C
with 10% patient serum (t = 8 hours). Migration was quantified
using ImageJ where the denuded area at t = 8 hours was sub-
tracted from the denuded area at t = 0 hour to calculate percent
area closed. The average of each sample (triplicate) was used
for analysis.
Cell Proliferation: BrdU Incorporation
Contact inhibited HPMECs were seeded in a 96-well plate
(5 £ 103
cells/well), allowed to attach, serum-starved overnight
in 0.5% FBS and then incubated with 10% patient serum.
BrdU was added directly to each well and incubated for
24 hours. After a total of 48-hour incubation with patient
serum, cells were fixed and immunostained according to the
manufacturer’s recommendations (Roche, #11647229001).
The average of each sample (triplicate) was used for statistical
analysis and is reported relative to control (HPMEC treated
with complete growth medium).
Cell Proliferation: Cell Cycle Analysis
Contact inhibited HPMECs were seeded in 6-well plates
(2.5 £ 105
cells/well), allowed to attach, serum-starved over-
night in 0.5% FBS, and then incubated with 10% patient serum
for a total of 48 hours. Serum-treated cells were then trypsi-
nized and incubated with LIVE/DEAD yellow dead cell stain
kit (ThermoFisher, #L34968). After surface staining with via-
bility dye, cells were washed, fixed and permeabilized with BD
Pharmingen Transcription-Factor buffer set (BD Biosciences,
#562574), and DNA was stained with propidium iodide (BD
Biosciences, #550825). Samples were acquired on a BD For-
tessa flow cytometer and data were analyzed with FlowJo soft-
ware (version 10.5.3). Only viable cells (negative for yellow
dead cell stain) were used for cell cycle quantification.
Apoptosis: Caspase 3/7 Activity
Contact inhibited HPMECs were seeded in a 96-well plate
(5 £ 103
cells/well), allowed to attach, serum-starved overnight
in 0.5% FBS, and then incubated with 10% patient serum for a
total of 48 hours. Caspase 3/7 substrate was directly added to
each well and incubated at room temperature for 6 hours.
Fluorescent caspase 3/7 activity was determined according to
the manufacturer’s recommendations (Promega, #G7790). The
average of each sample (triplicate) was used for statistical analy-
sis and is reported relative to control (HPMEC treated with
complete growth medium).
Apoptosis: Annexin-V Labeling
Contact inhibited HPMECs were seeded in 6-well plates
(2.5 £ 105
cells/well), allowed to attach, serum-starved over-
night in 0.5% FBS, and then incubated with 10% patient serum
for a total of 48 hours. Serum-treated cells were then trypsi-
nized and incubated with LIVE/DEAD yellow dead cell stain
kit (ThermoFisher, #L34968). After surface staining with
viability dye, cells were washed and incubated with Annexin
V-PE conjugate (BD Biosciences, #563544). Samples were
acquired on a BD Fortessa flow cytometer and data were ana-
lyzed with FlowJo software (version 10.5.3). Viable cells (nega-
tive for yellow dead cell stain) with positive Annexin-V
staining specifically represent apoptotic cells and were used for
apoptosis quantification.
Statistical Analysis
Patient demographics are summarized as median (range) for
continuous data and n (%) for categorical data. Wilcoxon
signed-rank test, a nonparametric method, was used for com-
parisons between HV and SVC. Differences in medians with
95% confidence intervals (CI) for the observed differences in
median levels were estimated using the Hodges-Lehmann
method. For single experiments with multiple outcomes (tube
formation assay and cell cycle analysis), we adjusted for multi-
ple comparisons using false discovery rate (FDR) correction.
Potential outliers were identified as outside of lower quartile À
(1.5£ interquartile range) and upper quartile + (1.5£ inter-
quartile range). To investigate whether the results were
impacted by patients’ demographics and clinical variables, we
performed repeated measures analysis with the following cova-
riates included separately or together: age, gender, SpO2, hyp-
oxia (94% vs ≥94%), PAVMs (yes vs no), univentricular (yes
vs no), and biventricular circulation with left-to-right shunt
(yes vs no). Statistical significance was accepted at the level of
P 0.05 or FDR-adjusted P 0.05. All analyses were per-
formed using SAS 9.4 (SAS Institute, Cary, NC), StatXact 8,
and GraphPad Prism 8 (GraphPad Software, San Diego, CA).
RESULTS
Patient Characteristics
Blood samples from 32 patients at Children’s Hospital of
Wisconsin were included. Patient age ranged from 3 months to
10 years with a median age of 29 months. Eighteen patients
(56%) were female. SpO2 ranged 79À100% with a median
SpO2 of 97%; 12 patients (38%) had SpO2 94%. Patient dem-
ographics, including primary cardiac diagnosis are summarized
in Table. PAVMs were diagnosed or suspected in 7/32 patients
(21.9%). Two patients with univentricular circulation were not
suspected to have PAVMs due to normal SpO2 (95%) in 1
patient status post-TCPC and 1 patient who underwent cardiac
catheterization pre-SCPC. Experimental results from specific
patient groups are reported in Supplemental Figures 1À4.
HV Serum Increased Tube Formation and Cell
Migration of HPMECs In Vitro
HV serum increased HPMEC tube formation and cell migra-
tion compared to SVC serum in vitro (Fig. 1). HV serum
increased multiple parameters of tube formation compared to
SVC serum, including number of nodes (median difference
(HV-SVC) 0.07, 95% CI for median difference 0.02, 0.17;
P = 0.02; FDR-adjusted P = 0.04), number of tubes (median
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Seminars in Thoracic and Cardiovascular Surgery Volume 00, Number 00 3
4. difference 0.10, 95% CI 0.01, 0.21; P = 0.03; FDR-adjusted
P = 0.04), and tube length (median difference 0.08, 95% CI
0.004, 0.18; P = 0.04; FDR-adjusted P = 0.04; n = 24 for all
parameters; Fig. 1AÀE). HV serum also increased HPMEC
wound closure compared to SVC serum using the scratch
migration assay (median difference 0.03, 95% CI 0.02, 0.06; P
0.001; n = 18; Fig. 1FÀJ). After adjusting for single and mul-
tiple patient variables, the differences in tube formation and
scratch migration between HV and SVC remained statistically
significant (Supplementary Table 1). Three potential outliers
were identified in the tube formation assay. Patients included a
15-month-old male with patent ductus arteriosus (PDA) and
normal SpO2 (98%), a 35-month-old female with PDA and
normal SpO2 (98%), and a 57-month-old female with history
of ventricular septal defect and pulmonary hypertension on
pulmonary vasodilator therapy with normal SpO2 (95%). No
outliers were identified in the scratch migration assay.
Table. Patient Demographics
Female Patients, n (%) 18 (56.3)
Age (mo), median (range) 29 (3À126)
SpO2 (%), median (range) 97 (79À100)
Primary cardiac diagnosis,
n (%)
Functionally univentricular, 9 (28.1)
Patent ductus arteriosus, 5 (15.6)
Tetralogy of Fallot, 4 (12.5)
Pulmonary valve stenosis, 4 (12.5)
Atrial septal defect, 2 (6.3)
Ventricular septal defect, 2 (6.3)
Atrioventricular septal defect, 2 (6.3)
Pulmonary hypertension, 2 (6.3)
Double outlet right ventricle, 1 (3.1)
Coarctation of aorta, 1 (3.1)
Type of functionally
univentricular, n (%)
Double inlet left ventricle, 1 (11)
Double outlet right ventricle, 1 (11)
Hypoplastic left heart syndrome, 5 (56)
Tricuspid atresia, 2 (22)
SpO2, peripheral oxygen saturation.
Figure 1. HV serum increases HPMEC angiogenic activity compared to SVC serum. (AÀC) Quantification of HPMEC tube formation
after 4-hour incubation with HV or SVC serum. N = 24 per group. Before and after plots represent individual patient samples with
lines connecting paired samples. (D, E) Representative images of tube formation. (F) Quantification of HPMEC migration 8 hours
after scratch migration assay. N = 18 per group. Before and after plot represents individual patient samples with lines connecting
paired samples. (GÀJ) Representative images of scratch migration at 0 hours (T = 0 hour) and 8 hours (T = 8 hours). Scale bars rep-
resent 200 mm. HPMEC, human pulmonary microvascular endothelial cells; HV, hepatic vein; SVC, superior vena cava.
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4 Seminars in Thoracic and Cardiovascular Surgery Volume 00, Number 00
5. HV Serum Promoted HPMEC Survival Through
Increased Proliferation and Decreased Apoptosis
After incubating HPMECs with HV or SVC serum for
48 hours, HPMECs exposed to HV serum had more prolifera-
tion (Fig. 2) and less apoptosis (Fig. 3) than HPMECs exposed
to paired SVC serum samples. HV serum increased BrdU incor-
poration (median difference 0.10, 95% CI 0.05, 0.15; P 0.001;
n = 32) relative to control (Fig. 2A). HV serum also increased the
percentage of HPMECs in S-phase of the cell cycle (median dif-
ference 0.4, 95% CI 0.02, 0.7; P = 0.04; FDR-adjusted P = 0.04;
n = 13), increased the percentage in G2-M phases (median differ-
ence 0.65, 95% CI 0.04, 1.74; P = 0.02; FDR-adjusted P = 0.03;
n = 13), and decreased the percentage in G1-G0 phases (median
difference À1.16, 95% CI À2.34, À0.20; P = 0.01; FDR-
adjusted P = 0.03; n = 13; Fig. 2BÀD). After adjusting for single
and multiple patient variables, the differences in BrdU incorpo-
ration and percentage of cells in G1-G0 phases between HV and
SVC remained statistically significant. Percentage of cells in S-
phase remained significant after adjusting for single patient vari-
ables but not multiple patient variables. The difference in per-
centage of cells in G2-M phase of the cell cycle was not
statistically significant when single and multiple covariates were
included (Supplementary Table 2). No outliers were identified
in the BrdU incorporation assay. One potential outlier was iden-
tified in the cell cycle analysis—a 28-month-old female with
PDA and normal SpO2 (99%).
HV serum decreased activity of caspase 3 and 7 (median dif-
ference À0.14, 95% CI À0.21, À0.07; P 0.001; n = 32) rela-
tive to control (Fig. 3A). HV serum also decreased the
percentage of Annexin-V positive cells (median difference
À1.11, 95% CI À2.11, À0.03; P = 0.04; n = 12; Fig. 3BÀD).
After adjusting for patient variables, the differences in caspase
3/7 activity and Annexin-V positive cells between HV and SVC
remained statistically significant (Supplementary Table 3). No
outliers were identified in the caspase activity assay or
Annexin-V assay.
Figure 2. HV serum increases HPMEC proliferation compared to SVC serum. (A) Quantification of HPMEC proliferation using color-
imetric absorbance of BrdU incorporation. N = 32 per group. Before and after plot represents individual patient samples with lines
connecting paired patient samples. (B) Quantification of HPMEC proliferation using cell cycle analysis with PI as detected by flow
cytometry. N = 13 per group. Before and after plots represent individual patient samples with lines connecting paired patient sam-
ples. (C, D) Representative histograms of cell cycle analysis. HPMEC, human pulmonary microvascular endothelial cells; HV,
hepatic vein; PI, propidium iodine; SVC, superior vena cava.
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Seminars in Thoracic and Cardiovascular Surgery Volume 00, Number 00 5
6. DISCUSSION
In this study, we demonstrate that venous blood from differ-
ent anatomic sources differentially impacts the pulmonary vas-
culature (Fig. 4). Specifically, in static cell culture conditions,
HV serum regulates HPMECs differently than SVC serum by
increasing angiogenesis and cell survival. Our study reports a
novel approach to investigate the etiology and pathogenesis of
CHD-associated PAVMs. By specifically testing paired blood
samples from the HV and SVC from children with CHD, we
aim to improve our understanding of the precise roles of HV
and SVC blood in CHD-associated PAVMs independent of
blood flow. Greater understanding of HV blood and CHD-
associated PAVMs may allow accurate identification of hepatic
factor and subsequent development of targeted molecular-
based therapies.
There are several salient features of our study, which we will
compare and contrast below with the published literature. Our
data indicate that HV serum increases HPMEC angiogenesis in
vitro compared to SVC serum, which differs from previous
studies.14,17À19
Angiogenesis is a dynamic, context-dependent,
multistaged process. Thus, differing experimental results from
other studies are not surprising. Kavarana et al investigated
angiogenic changes after SCPC using a pig model of SCPC
physiology (“classic Glenn”—end-to-end SVC to right pulmo-
nary artery anastomosis).14
They harvested pulmonary artery
Figure 3. HV serum decreases HPMEC apoptosis compared to SVC serum. (A) Quantification of HPMEC apoptosis using fluores-
cence of caspase 3 and caspase 7 activity. N = 32 per group. (B) Quantification of apoptosis using Annexin-V labeling of apoptotic
cells as detected by flow cytometry. N = 12 per group. Before and after plots represent individual patient samples with lines con-
necting paired patient samples. (C, D) Representative scatter plots of Annexin-V staining (x-axis) and cell viability staining (y-axis)
to quantify apoptotic HPMECs. HPMEC, human pulmonary microvascular endothelial cells; HV, hepatic vein; SVC, superior vena
cava.
Figure 4. Patient-derived venous blood samples obtained from
the HV and SVC differentially impacts the lung microvascula-
ture in vitro. Differential regulation of microvascular endothelial
cell angiogenesis (tube formation and migration), proliferation,
and apoptosis can lead to lung microvascular remodeling and
subsequent PAVM formation. HV, hepatic vein; PAVM, pulmo-
nary arteriovenous malformation; SVC, superior vena cava.
CONGENITAL À Original Submission
6 Seminars in Thoracic and Cardiovascular Surgery Volume 00, Number 00
7. ECs 6À8 weeks after SCPC by scraping the luminal surface of
the branch pulmonary artery and culturing these macrovascu-
lar ECs. With the cultured ECs, they performed tube formation
assays and reported increased number of tubes and tube length
in ECs from the lung receiving exclusive SVC blood flow.
Importantly, their study used ECs from a large branch pulmo-
nary artery (macrovascular) rather than microvascular ECs,
which are the affected ECs in PAVM pathophysiology. Addi-
tionally, as previously stated, it is unknown whether the
increased tube formation is due to lack of HV blood (ie, hepatic
factor) perfusing the lungs or whether it is due to change from
pulsatile to nonpulsatile blood flow.
Using patient lung biopsies after SCPC, Duncan et al reported
initial findings from 2 patients, and Starnes et al subsequently
reported follow-up findings from 8 and 13 patients.17À19
Their
histologic studies used immunostaining with von Willebrand
factor to determine microvessel density.17,18
Microvessel density
is often used as a surrogate marker for angiogenesis by quantify-
ing microvascular ECs per surface area.20
Duncan et al found
that patients after SCPC had increased von Willebrand factor
staining compared to controls in the initial and follow-up study.
They concluded that lack of HV blood flow to the lungs
increased microvessel density and thus increased angiogenesis,
which is in contrast to our findings. Importantly, Starnes et al
insightfully acknowledged that SCPC may cause PAVMs due to
abnormal angiogenesis and vascular remodeling.18
This is sup-
ported by their data. In the initial study, Duncan et al reported
diminished CD31 staining, and Starnes et al confirmed
decreased CD31 staining in the follow-up study.17,19
Paradoxi-
cally, CD31 is also accepted as an immunostaining marker for
microvessel density.20
Thus, 2 different EC markers for micro-
vessel density give different results from the same histologic
samples. These differences exemplify that angiogenesis is a
dynamic multifaceted process of remodeling that occurs both
physiologically and pathologically. While our data do not fully
reconcile with these previous studies, our findings are in agree-
ment with the interpretation that vascular remodeling is likely
altered in PAVM pathophysiology.
An important component of angiogenesis and vascular
remodeling is the balance of EC proliferation and apoptosis.
One of the initial studies investigating hepatic factor and CHD-
associated PAVMs reported that hepatocyte-conditioned media
inhibited pulmonary artery EC proliferation.16
This finding is
consistent with the data reported by Kavarana et al.14
Kavarana
et al reported that exclusive SVC blood flow in their pig model
of SCPC physiology increased pulmonary artery EC proliferation
compared to control ECs.14
These results are in contrast to our
finding that HV serum increases HPMEC proliferation compared
to SVC serum. Again, several major differences may account for
these discrepancies: species (human vs pig), cell type (pulmo-
nary artery macrovascular ECs vs lung microvascular EC), and
flow (nonpulsatile blood flow vs static cell culture).
In contrast to Kavarana et al, Duncan and Starnes also investi-
gated EC proliferation using lung biopsies obtained from chil-
dren after SCPC.17,19
They used immunostaining with
proliferating cell nuclear antigen to assess proliferation. They
reported no differences in proliferating cell nuclear antigen stain-
ing between patients after SCPC and age-matched controls.
These findings are also in contrast to our data because they
reported no difference in proliferation, rather than decreased
proliferation after SCPC. Without longitudinal assessments, we
cannot determine if there are differences in EC proliferation at
different stages of PAVM progression or resolution.
In terms of apoptosis, we demonstrate that HV serum
decreases HPMEC apoptosis compared to SVC serum. To our
knowledge, no previous studies of CHD-associated PAVMs
directly investigated apoptosis. Malhotra et al reported an inter-
esting finding of increased EC oxidative stress 2 and 5 weeks
after SCPC.15
In their study, they compared lambs that under-
went SCPC (“classic Glenn”), a unilateral branch PA band, or
sham surgery. They reported that both SCPC and PA band
increased angiogenic gene expression in whole lung lysates.
On the other hand, SCPC increased EC stress response (heme-
oxygenase 1, GLUT1, CD62), but PA band and sham did not.
They concluded that endothelial stress response may be more
relevant to PAVM formation than an angiogenic response. We
speculate that our observed differences in apoptosis reflect a
manifestation of SVC blood-induced EC stress.
Because PAVM formation is a dynamic process of vascular
remodeling, direct comparison between our findings and previ-
ous animal models of SCPC should be interpreted cautiously.
Our results represent the effects of patient serum on quiescent
lung microvascular ECs after 48 hours of exposure, which differs
from the longer term exposure with animal models of SCPC
(2À8 weeks). A snapshot of the lung microvasculature after
PAVM formation in vivo may represent a different stage of vascu-
lar remodeling compared to our in vitro findings. Additionally,
our patient blood samples were obtained from a heterogeneous
cohort at a single time-point. We cannot determine if the serum
constituents in our patient samples primarily regulate the pulmo-
nary microvasculature or if our patients’ serum contains factors
that are upregulated or downregulated in compensation for
remodeling pulmonary vasculature. Finally, we attempted to
investigate how patient variables impacted our results using
repeated measures analysis. These subanalyses showed similar
results with the exception of cell cycle analysis, which was per-
formed with fewer patient samples. Ultimately, though, our anal-
yses were limited to overall small patient numbers.
Despite previous data and our observations, there are many
unknowns in the pathogenesis of CHD-associated PAVMs. We
hypothesize that PAVMs develop following SCPC because (1)
exclusive SVC blood flow causes increased cellular stress due
to inflammatory and pro-apoptotic signals in SVC blood and
loss of physiologic growth factors in HV blood. Chronically,
decreased exposure of the pulmonary microvasculature to
physiologic growth factors and increased EC stress leads to
maladaptive microvascular remodeling and pathologic angio-
genesis. Alternative etiologies are possible, though. For exam-
ple, (2) HV blood may contain an inhibitory factor that
maintains microvascular EC homeostasis by suppressing
CONGENITAL À Original Submission
Seminars in Thoracic and Cardiovascular Surgery Volume 00, Number 00 7
8. proliferation and angiogenesis. Exclusion of this factor from the
pulmonary vascular bed (ie, SCPC circulation) dysregulates the
pulmonary microvasculature and leads to PAVM formation. (3)
HV blood may contain a set of factors—both physiologic
growth factors and inhibitory factors that regulate pulmonary
microvascular homeostasis. Redundant factors may help
explain the variability in PAVM severity. (4) HV and SVC blood
may not directly regulate pulmonary microvascular ECs.
Rather, HV blood may regulate vascular support cells (smooth
muscle cells and pericytes) and the extracellular matrix, which
provide the necessary scaffold for ECs. Loss of the vascular
scaffold leads to vascular remodeling and PAVM formation. (5)
Finally, multiple studies indicate the flow plays a role in vascu-
lar homeostasis.21À23
Resolution of PAVMs after TCPC pallia-
tion suggests that hepatic factor functions independent of flow;
however, we cannot exclude that flow has a role in pulmonary
vascular remodeling and PAVMs. Thus, our study in the con-
text of the literature implicates that vascular remodeling is a
key event in PAVM pathogenesis. Further ongoing studies will
clarify the underlying mechanisms.
CONCLUSION
In static cell culture conditions, HV serum regulates HPMECs
differently than SVC serum by increasing angiogenesis and cell sur-
vival. Loss of HV serum signaling in the lung microvasculature,
which occurs with SCPC circulation, may promote lung microvas-
cular remodeling and PAVM formation. The specific constituents
of HV and SVC serum that mediate these effects, and whether these
changes occur in vivo, requires further investigation.
Acknowledgments
We thank members of the Developmental Vascular Biology
lab, Pediatric Cardiology Division, Herma Heart Institute, and
MCW Cardiovascular Center for their input. We sincerely
acknowledge the generous contribution of patients and families
to this study, as well as the staff of the Cardiac Catheterization
Lab who assisted in sample collection.
SUPPLEMENTARY MATERIAL
Supplementary material associated with this article can be found
in the online version at doi:10.1053/j.semtcvs.2020.03.004.
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