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.
This study evaluated the outcomes of 23 patients presenting with pulseless electrical activity (PEA) due to confirmed pulmonary embolism (PE) who were treated with thrombolysis. All patients received 50 mg of tissue plasminogen activator (tPA) intravenously during ongoing cardiopulmonary resuscitation (CPR). Return of spontaneous circulation occurred in most patients within 15 minutes of tPA administration. At a mean follow up of 22 months, 20 of the 23 patients (87%) were still alive with significant reductions in pulmonary artery pressures and right ventricular enlargement. The study demonstrated that rapid administration of low-dose tPA during CPR for PEA due to PE is safe and effective for restoring circulation and
Transcatheter intraarterial infusion of rt pa forHans Garcia
This study evaluated the success and complication rates of using intraarterial recombinant tissue-type plasminogen activator (rt-PA) infusion to treat acute lower extremity artery and bypass graft occlusions in 74 limbs of 70 patients. Thrombolytic success, defined as 95% thrombolysis and return of blood flow, was achieved in 86% of cases. Major bleeding complications occurred in 47% of patients, including bleeding at vascular access sites in 22 patients and remote bleeding in 7 patients. Despite the significant bleeding complications, 30-day mortality was 1% and amputation rate was 6%, resulting in a favorable 30-day amputation-free survival rate of 93%.
ACTEP2014: Sepsis management has anything change taem
This document discusses sepsis management and what has changed. It begins with an introduction to the pathophysiology of sepsis, severe sepsis, and septic shock. It then discusses early goal directed therapy (EGDT) and landmark studies like Rivers 2001 that promoted protocolized resuscitation to targets like central venous pressure, mean arterial pressure, ScvO2, and transfusion thresholds. However, later large trials like ProCESS 2014 found no difference in mortality between EGDT, standard therapy, and usual care. Targets like CVP are not accurate predictors of fluid responsiveness. Studies also found no difference in outcomes between higher and lower blood pressure or hemoglobin transfusion thresholds. There remains uncertainty around optimal fluid type, vas
Critical appraisal of Stitch Trial by Dr. Akshay Mehtacardiositeindia
The STICH trial tested two hypotheses regarding the treatment of ischemic heart failure:
1) Adding CABG to medical therapy improves long-term survival more than medical therapy alone.
2) For patients with anterior left ventricular dysfunction, surgical ventricular reconstruction plus CABG and medical therapy improves survival free of cardiac hospitalization more than CABG and medical therapy without ventricular reconstruction. The trial randomized over 1200 patients to test these hypotheses but did not find conclusive evidence to support either the primary or secondary hypotheses.
This document discusses several novel biomarkers for acute coronary syndrome (ACS). It describes C-reactive protein (CRP) as a marker of extensive vascular inflammation. High-sensitivity CRP levels above 10 mg/L are more predictive of outcomes in ACS patients. Soluble CD40 ligand and myoglobin are also discussed as inflammation markers. Microalbuminuria is related to endothelial dysfunction and an increased risk of cardiovascular disease. Cystatin C and metalloproteinases are associated with arterial stiffness and plaque degradation. Several microRNAs such as miR-1, miR-133 and miR-208 are described as potential biomarkers for myocardial infarction, cardiac hypertrophy, and arrhythmias.
The document discusses chronic thromboembolic pulmonary hypertension (CTEPH) and its pathophysiology. It describes the core pathologic process as an imbalance between prothrombotic factors and disturbed thrombus resolution, leading to in situ thrombosis over thromboembolic lesions. It also discusses the BENEFIT trial which found that treatment with bosentan improved exercise capacity and hemodynamics in inoperable CTEPH patients. The CHEST trial then evaluated riociguat, a soluble guanylate cyclase stimulator, in inoperable or recurrent CTEPH patients and found improvements in pulmonary vascular resistance and other outcomes.
The field of perfusion is becoming increasingly demanding both clinically and didactically. As the patient population continues to present with a variety of complex health issues, there is a greater need than ever for the Pefusionist to develop new techniques for patient care while on Cardiopulmonary Support. Ascending Aortic Arch dissections (AAAD), with its current mortality rates of 10%-15% with significant neurological complications associated, still remains a difficult case for Perfusionist’s to manage effectively. The most widely used technique during this type of repair surgery, is hypothermic circulatory arrest (HCA). Although this remains a premier technique, there continues to be a high reported incidence of neurological deficit post HCA. In order to address and limit this issue, the advent of selective cerebral perfusion is slowly gaining acceptance. This new technique has been shown to not only decrease the time of exposure of blood to a foreign surface, but limit the patient duration on full cardiopulmonary support. The most notable aspect of this technique; is it allows the surgeon to begin repairs immediately, since the process cools the brain only, while keeping the rest of body at moderate-mild hypothermic levels.
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.
This study evaluated the outcomes of 23 patients presenting with pulseless electrical activity (PEA) due to confirmed pulmonary embolism (PE) who were treated with thrombolysis. All patients received 50 mg of tissue plasminogen activator (tPA) intravenously during ongoing cardiopulmonary resuscitation (CPR). Return of spontaneous circulation occurred in most patients within 15 minutes of tPA administration. At a mean follow up of 22 months, 20 of the 23 patients (87%) were still alive with significant reductions in pulmonary artery pressures and right ventricular enlargement. The study demonstrated that rapid administration of low-dose tPA during CPR for PEA due to PE is safe and effective for restoring circulation and
Transcatheter intraarterial infusion of rt pa forHans Garcia
This study evaluated the success and complication rates of using intraarterial recombinant tissue-type plasminogen activator (rt-PA) infusion to treat acute lower extremity artery and bypass graft occlusions in 74 limbs of 70 patients. Thrombolytic success, defined as 95% thrombolysis and return of blood flow, was achieved in 86% of cases. Major bleeding complications occurred in 47% of patients, including bleeding at vascular access sites in 22 patients and remote bleeding in 7 patients. Despite the significant bleeding complications, 30-day mortality was 1% and amputation rate was 6%, resulting in a favorable 30-day amputation-free survival rate of 93%.
ACTEP2014: Sepsis management has anything change taem
This document discusses sepsis management and what has changed. It begins with an introduction to the pathophysiology of sepsis, severe sepsis, and septic shock. It then discusses early goal directed therapy (EGDT) and landmark studies like Rivers 2001 that promoted protocolized resuscitation to targets like central venous pressure, mean arterial pressure, ScvO2, and transfusion thresholds. However, later large trials like ProCESS 2014 found no difference in mortality between EGDT, standard therapy, and usual care. Targets like CVP are not accurate predictors of fluid responsiveness. Studies also found no difference in outcomes between higher and lower blood pressure or hemoglobin transfusion thresholds. There remains uncertainty around optimal fluid type, vas
Critical appraisal of Stitch Trial by Dr. Akshay Mehtacardiositeindia
The STICH trial tested two hypotheses regarding the treatment of ischemic heart failure:
1) Adding CABG to medical therapy improves long-term survival more than medical therapy alone.
2) For patients with anterior left ventricular dysfunction, surgical ventricular reconstruction plus CABG and medical therapy improves survival free of cardiac hospitalization more than CABG and medical therapy without ventricular reconstruction. The trial randomized over 1200 patients to test these hypotheses but did not find conclusive evidence to support either the primary or secondary hypotheses.
This document discusses several novel biomarkers for acute coronary syndrome (ACS). It describes C-reactive protein (CRP) as a marker of extensive vascular inflammation. High-sensitivity CRP levels above 10 mg/L are more predictive of outcomes in ACS patients. Soluble CD40 ligand and myoglobin are also discussed as inflammation markers. Microalbuminuria is related to endothelial dysfunction and an increased risk of cardiovascular disease. Cystatin C and metalloproteinases are associated with arterial stiffness and plaque degradation. Several microRNAs such as miR-1, miR-133 and miR-208 are described as potential biomarkers for myocardial infarction, cardiac hypertrophy, and arrhythmias.
The document discusses chronic thromboembolic pulmonary hypertension (CTEPH) and its pathophysiology. It describes the core pathologic process as an imbalance between prothrombotic factors and disturbed thrombus resolution, leading to in situ thrombosis over thromboembolic lesions. It also discusses the BENEFIT trial which found that treatment with bosentan improved exercise capacity and hemodynamics in inoperable CTEPH patients. The CHEST trial then evaluated riociguat, a soluble guanylate cyclase stimulator, in inoperable or recurrent CTEPH patients and found improvements in pulmonary vascular resistance and other outcomes.
The field of perfusion is becoming increasingly demanding both clinically and didactically. As the patient population continues to present with a variety of complex health issues, there is a greater need than ever for the Pefusionist to develop new techniques for patient care while on Cardiopulmonary Support. Ascending Aortic Arch dissections (AAAD), with its current mortality rates of 10%-15% with significant neurological complications associated, still remains a difficult case for Perfusionist’s to manage effectively. The most widely used technique during this type of repair surgery, is hypothermic circulatory arrest (HCA). Although this remains a premier technique, there continues to be a high reported incidence of neurological deficit post HCA. In order to address and limit this issue, the advent of selective cerebral perfusion is slowly gaining acceptance. This new technique has been shown to not only decrease the time of exposure of blood to a foreign surface, but limit the patient duration on full cardiopulmonary support. The most notable aspect of this technique; is it allows the surgeon to begin repairs immediately, since the process cools the brain only, while keeping the rest of body at moderate-mild hypothermic levels.
1. The study examined the incidence of junctional ectopic tachycardia (JET) in 343 patients after surgery for congenital heart defects.
2. JET occurred in 37 patients (10.8%), most frequently after repair of tetralogy of Fallot. JET significantly increased ventilation time and intensive care unit stay.
3. Treatment for JET, including surface cooling and amiodarone, was associated with further increases in ventilation time and intensive care unit stay, though it successfully converted the arrhythmia in most patients.
Patient with chronic PE treatment options - dr Szymon Darochapiodof
This document discusses treatment options for a 52-year-old female patient with chronic thromboembolic pulmonary hypertension (CTEPH) who is not eligible for pulmonary endarterectomy surgery. It provides background on CTEPH, describes the patient's condition and past treatment history, and reviews the potential for balloon pulmonary angioplasty (BPA) as an alternative treatment approach. BPA involves using a balloon catheter to break up clots and scar tissue in the lungs and has shown promising results in some CTEPH patients who cannot undergo surgery. The document also shares early experience with BPA from another medical center and reviews its safety profile.
This document summarizes a study exploring the roles of intrinsic myocardial systolic dysfunction and cardiac chamber dilatation in left ventricular pump dysfunction following chronic beta-adrenergic receptor activation in rats. The study found that chronic isoproterenol administration resulted in left ventricular pump dysfunction, as evidenced by reduced fractional shortening and decreased slope of the pressure-volume relation, despite normal intrinsic myocardial contractility. Pump failure was attributed to left ventricular dilatation rather than intrinsic systolic failure, as midwall fractional shortening and stress-strain relations were unchanged.
1. A study found that early treatment of a first episode of acute pericarditis with colchicine in addition to standard anti-inflammatory therapy reduced the risk of recurrence compared to anti-inflammatory therapy alone.
2. The STOP-HF trial found that screening high-risk patients for heart failure with BNP and providing further assessment and care for those with elevated BNP resulted in less left ventricular dysfunction, heart failure, and emergency hospitalizations compared to usual care.
3. The EchoCRT trial of CRT in patients with narrow QRS found no benefit of CRT and more deaths with CRT, suggesting CRT is not recommended for patients with narrow QRS.
This document discusses renal denervation as a treatment for modulating autonomic functions. It first provides background on renal denervation and its proof of principle in reducing sympathetic nerve activity and blood pressure in resistant hypertension patients. It then summarizes staged clinical trials that demonstrate efficacy and safety. The remainder explores potential applications of renal denervation in glucose metabolism, obstructive sleep apnea, heart failure, and neurovascular control of dyspnea. A small safety study in heart failure patients showed improvements in 6-minute walk distance after renal denervation.
The STITCH trial evaluated the effect of CABG plus optimal medical therapy (OMT) versus OMT alone on mortality in patients with left ventricular dysfunction and coronary artery disease. A sub-study examined the role of assessing myocardial viability to identify patients who benefit most from CABG. Of 601 patients who underwent viability testing, 487 had viable myocardium and 114 did not. There was no significant interaction between viability status and treatment assignment on mortality or other outcomes. Assessing viability did not identify patients with differential survival benefit from CABG versus OMT alone.
This document summarizes information on anemia in heart failure patients. Some key points:
1. The prevalence of anemia in heart failure patients ranges from 20-30% for outpatients to 30-40% for inpatients, depending on the definition and study.
2. Anemia is associated with worse prognosis and increased risk of hospitalization and mortality in heart failure patients.
3. Potential treatment options for anemia in heart failure include blood transfusions, erythropoietin-stimulating proteins (ESPs), and iron therapy. However, clinical trials of ESPs like darbepoetin alfa have not shown clear benefits.
4. The FAIR-HF trial found
Myocardial viability testing all STICHed up, or about to be REVIVEDNicolas Ugarte
Patients with ischaemic left ventricular dysfunction frequently undergo myocardial viability testing. The historical model presumes that
those who have extensive areas of dysfunctional-yet-viable myocardium derive particular benefit from revascularization, whilst those without extensive viability do not. These suppositions rely on the theory of hibernation and are based on data of low quality: taking a dogmatic
approach may therefore lead to patients being refused appropriate, prognostically important treatment. Recent data from a sub-study of
the randomized STICH trial challenges these historical concepts, as the volume of viable myocardium failed to predict the effectiveness of
coronary artery bypass grafting. Should the Heart Team now abandon viability testing, or are new paradigms needed in the way we interpret viability? This state-of-the-art review critically examines the evidence base for viability testing, focusing in particular on the presumed
interactions between viability, functional recovery, revascularization and prognosis which underly the traditional model. We consider
whether viability should relate solely to dysfunctional myocardium or be considered more broadly and explore wider uses of viability testingoutside of revascularization decision-making. Finally, we look forward to ongoing and future randomized trials, which will shape evidence-based clinical practice in the futur
Imaging techniques for myocardial hibernationMichael Katz
1) Imaging techniques can help assess myocardial viability, metabolism, perfusion, and function to help determine if dysfunctional heart muscle following a heart attack is still viable or permanently damaged.
2) Viable heart muscle may be stunned, hibernating, or have experienced a partial thickness heart attack, and imaging can help distinguish these states and identify areas that could recover with revascularization.
3) The document reviews definitions and pathophysiology of myocardial hibernation, viability, stunned myocardium, and discusses the utility of various imaging modalities and EKG findings for assessing viability and predicting recovery of heart function.
1) A study examined 103 heart attack patients treated with high-dose statins and found plaque volume decreased slightly (0.9%) in the arteries not responsible for the heart attack.
2) A randomized study of 296 heart attack patients found that performing revascularization of additional blocked arteries beyond the heart attack artery led to fewer total cardiac events (10% vs 21%) over 12 months compared to only treating the heart attack artery.
3) A study of 738 patients with chronic total blockages and good collateral blood flow found that revascularizing the blockages reduced cardiac death and total cardiac events compared to medical treatment alone, showing benefit of revascularization even in patients with established collateral circulation.
Novel paclitaxel coated balloon - dr Piotr Buszmanpiodof
This document summarizes a clinical trial evaluating a novel microcrystalline paclitaxel coated balloon (mcPCB, PAX) for the treatment of femoropopliteal restenosis. The trial aims to evaluate the safety and efficacy of the mcPCB compared to uncoated balloons or standard care. It will be a multicenter, randomized controlled trial enrolling patients with claudication due to restenosis within a previously revascularized femoropopliteal segment. Previous studies on paclitaxel coated balloons showed reductions in restenosis compared to uncoated balloons. This novel mcPCB technology aims to provide a more consistent, uniform drug coating distribution compared to earlier generation
The document summarizes various strategies for managing thrombus burden during primary angioplasty for myocardial infarction. It discusses thrombus grading scales, the composition and types of thrombus, and the role of medications like GP IIb/IIIa inhibitors (abciximab, tirofiban, eptifibatide), heparin, and bivalirudin. It also compares intracoronary versus intravenous administration of these drugs and evaluates trials comparing different treatment strategies. Mechanical thrombectomy devices and a combined pharmacologic and mechanical approach are also reviewed.
This document discusses catecholaminergic polymorphic ventricular tachycardia (CPVT), a condition characterized by adrenergically mediated polymorphic ventricular arrhythmias without structural heart disease. It has a prevalence of 1 in 10,000 and mortality of up to 50% before age 20 if untreated. The gold standard for diagnosis is exercise stress testing showing exercise-induced bidirectional or polymorphic ventricular tachycardia. Treatment involves lifestyle changes, beta-blockers, flecainide, and an ICD for those with cardiac arrest or recurrent arrhythmias despite medical therapy. Genetic testing identifies mutations in RYR2 or CASQ2 genes in the majority of cases.
Ischaemic cardiomyopathy revascularisation how when and whycardiositeindia
This document discusses ischemic cardiomyopathy and revascularization. It begins with an overview of ischemic cardiomyopathy and discusses factors that contribute to left ventricular remodeling and heart failure progression. It then reviews data from studies such as the Duke CVD Data Bank and STITCH trial on the outcomes of coronary artery bypass grafting versus medical therapy for patients with ischemic cardiomyopathy. The document discusses the role of myocardial viability and hibernation in identifying patients most likely to benefit from revascularization. It reviews various modalities for assessing myocardial viability and hibernation such as cardiac MRI, PET, and echocardiography. Overall, the document provides an overview of ischemic cardiomyopathy and the evidence regarding revascularization outcomes based on viability assessment.
LCZ696 was more effective than enalapril in reducing the risks of CV death and HF hospitalization, CV death, HF hospitalization, and all-cause mortality in patients with heart failure with reduced ejection fraction. LCZ696 also provided incremental improvements in symptoms and physical limitations. LCZ696 was better tolerated than enalapril with lower rates of symptomatic hypotension, hyperkalemia, renal impairment, and cough.
Furosemide with matched hydration using the RenalGuard System was found to decrease the incidence of contrast-induced acute kidney injury (CI-AKI) compared to control treatments in patients undergoing interventional procedures. The RenalGuard System delivers intravenous fluids matched to urine output with hydration, furosemide, and continuous monitoring to maintain urine output over 300 ml/hr. A meta-analysis found the RenalGuard System reduced CI-AKI and need for renal replacement therapy with no increase in adverse events. However, more randomized trials are still needed to further evaluate the safety of the RenalGuard System.
Journal club multitarget therapy lupus nephritis maintenance chaken CHAKEN MANIYAN
Multitarget therapy of tacrolimus, mycophenolate mofetil and steroids achieved a 45.9% complete remission rate in induction treatment of lupus nephritis. This study assessed the efficacy of continuing multitarget therapy versus switching to azathioprine as maintenance treatment over 18 months. The cumulative renal relapse rate was lower in the multitarget group at 5.47% compared to 7.62% in the azathioprine group. More patients in the multitarget group maintained complete remission during maintenance treatment with no significant differences in safety profiles between the groups.
This document provides an overview of pulse oximetry and the oxyhemoglobin dissociation curve. It defines a pulse oximeter, describes how it works by measuring oxygenated and deoxygenated hemoglobin using light wavelengths, and notes that a normal oxygen saturation level is above 95%. The document also discusses the oxyhemoglobin dissociation curve and how shifts can occur, changing the relationship between oxygen in the blood and hemoglobin saturation. Common uses of pulse oximetry and potential limitations/interferences are outlined.
This document summarizes a study on using the dispersion width parameter (α in the Cole equation) measured through bioimpedance to monitor changes in living tissues. Through computer simulations and experiments on rat kidneys during cold preservation, the study finds:
1) The dispersion width could be determined by the morphology of the extra-cellular spaces.
2) Experiments show it is the only parameter able to detect conditions like warm ischemia prior to cold preservation or the effect of a drug disrupting the cytoskeleton.
3) The bioimpedance is useful not only for monitoring intra/extra-cellular volume but also for detecting tissue structural alterations, thanks to the dispersion width parameter.
1. The study examined the incidence of junctional ectopic tachycardia (JET) in 343 patients after surgery for congenital heart defects.
2. JET occurred in 37 patients (10.8%), most frequently after repair of tetralogy of Fallot. JET significantly increased ventilation time and intensive care unit stay.
3. Treatment for JET, including surface cooling and amiodarone, was associated with further increases in ventilation time and intensive care unit stay, though it successfully converted the arrhythmia in most patients.
Patient with chronic PE treatment options - dr Szymon Darochapiodof
This document discusses treatment options for a 52-year-old female patient with chronic thromboembolic pulmonary hypertension (CTEPH) who is not eligible for pulmonary endarterectomy surgery. It provides background on CTEPH, describes the patient's condition and past treatment history, and reviews the potential for balloon pulmonary angioplasty (BPA) as an alternative treatment approach. BPA involves using a balloon catheter to break up clots and scar tissue in the lungs and has shown promising results in some CTEPH patients who cannot undergo surgery. The document also shares early experience with BPA from another medical center and reviews its safety profile.
This document summarizes a study exploring the roles of intrinsic myocardial systolic dysfunction and cardiac chamber dilatation in left ventricular pump dysfunction following chronic beta-adrenergic receptor activation in rats. The study found that chronic isoproterenol administration resulted in left ventricular pump dysfunction, as evidenced by reduced fractional shortening and decreased slope of the pressure-volume relation, despite normal intrinsic myocardial contractility. Pump failure was attributed to left ventricular dilatation rather than intrinsic systolic failure, as midwall fractional shortening and stress-strain relations were unchanged.
1. A study found that early treatment of a first episode of acute pericarditis with colchicine in addition to standard anti-inflammatory therapy reduced the risk of recurrence compared to anti-inflammatory therapy alone.
2. The STOP-HF trial found that screening high-risk patients for heart failure with BNP and providing further assessment and care for those with elevated BNP resulted in less left ventricular dysfunction, heart failure, and emergency hospitalizations compared to usual care.
3. The EchoCRT trial of CRT in patients with narrow QRS found no benefit of CRT and more deaths with CRT, suggesting CRT is not recommended for patients with narrow QRS.
This document discusses renal denervation as a treatment for modulating autonomic functions. It first provides background on renal denervation and its proof of principle in reducing sympathetic nerve activity and blood pressure in resistant hypertension patients. It then summarizes staged clinical trials that demonstrate efficacy and safety. The remainder explores potential applications of renal denervation in glucose metabolism, obstructive sleep apnea, heart failure, and neurovascular control of dyspnea. A small safety study in heart failure patients showed improvements in 6-minute walk distance after renal denervation.
The STITCH trial evaluated the effect of CABG plus optimal medical therapy (OMT) versus OMT alone on mortality in patients with left ventricular dysfunction and coronary artery disease. A sub-study examined the role of assessing myocardial viability to identify patients who benefit most from CABG. Of 601 patients who underwent viability testing, 487 had viable myocardium and 114 did not. There was no significant interaction between viability status and treatment assignment on mortality or other outcomes. Assessing viability did not identify patients with differential survival benefit from CABG versus OMT alone.
This document summarizes information on anemia in heart failure patients. Some key points:
1. The prevalence of anemia in heart failure patients ranges from 20-30% for outpatients to 30-40% for inpatients, depending on the definition and study.
2. Anemia is associated with worse prognosis and increased risk of hospitalization and mortality in heart failure patients.
3. Potential treatment options for anemia in heart failure include blood transfusions, erythropoietin-stimulating proteins (ESPs), and iron therapy. However, clinical trials of ESPs like darbepoetin alfa have not shown clear benefits.
4. The FAIR-HF trial found
Myocardial viability testing all STICHed up, or about to be REVIVEDNicolas Ugarte
Patients with ischaemic left ventricular dysfunction frequently undergo myocardial viability testing. The historical model presumes that
those who have extensive areas of dysfunctional-yet-viable myocardium derive particular benefit from revascularization, whilst those without extensive viability do not. These suppositions rely on the theory of hibernation and are based on data of low quality: taking a dogmatic
approach may therefore lead to patients being refused appropriate, prognostically important treatment. Recent data from a sub-study of
the randomized STICH trial challenges these historical concepts, as the volume of viable myocardium failed to predict the effectiveness of
coronary artery bypass grafting. Should the Heart Team now abandon viability testing, or are new paradigms needed in the way we interpret viability? This state-of-the-art review critically examines the evidence base for viability testing, focusing in particular on the presumed
interactions between viability, functional recovery, revascularization and prognosis which underly the traditional model. We consider
whether viability should relate solely to dysfunctional myocardium or be considered more broadly and explore wider uses of viability testingoutside of revascularization decision-making. Finally, we look forward to ongoing and future randomized trials, which will shape evidence-based clinical practice in the futur
Imaging techniques for myocardial hibernationMichael Katz
1) Imaging techniques can help assess myocardial viability, metabolism, perfusion, and function to help determine if dysfunctional heart muscle following a heart attack is still viable or permanently damaged.
2) Viable heart muscle may be stunned, hibernating, or have experienced a partial thickness heart attack, and imaging can help distinguish these states and identify areas that could recover with revascularization.
3) The document reviews definitions and pathophysiology of myocardial hibernation, viability, stunned myocardium, and discusses the utility of various imaging modalities and EKG findings for assessing viability and predicting recovery of heart function.
1) A study examined 103 heart attack patients treated with high-dose statins and found plaque volume decreased slightly (0.9%) in the arteries not responsible for the heart attack.
2) A randomized study of 296 heart attack patients found that performing revascularization of additional blocked arteries beyond the heart attack artery led to fewer total cardiac events (10% vs 21%) over 12 months compared to only treating the heart attack artery.
3) A study of 738 patients with chronic total blockages and good collateral blood flow found that revascularizing the blockages reduced cardiac death and total cardiac events compared to medical treatment alone, showing benefit of revascularization even in patients with established collateral circulation.
Novel paclitaxel coated balloon - dr Piotr Buszmanpiodof
This document summarizes a clinical trial evaluating a novel microcrystalline paclitaxel coated balloon (mcPCB, PAX) for the treatment of femoropopliteal restenosis. The trial aims to evaluate the safety and efficacy of the mcPCB compared to uncoated balloons or standard care. It will be a multicenter, randomized controlled trial enrolling patients with claudication due to restenosis within a previously revascularized femoropopliteal segment. Previous studies on paclitaxel coated balloons showed reductions in restenosis compared to uncoated balloons. This novel mcPCB technology aims to provide a more consistent, uniform drug coating distribution compared to earlier generation
The document summarizes various strategies for managing thrombus burden during primary angioplasty for myocardial infarction. It discusses thrombus grading scales, the composition and types of thrombus, and the role of medications like GP IIb/IIIa inhibitors (abciximab, tirofiban, eptifibatide), heparin, and bivalirudin. It also compares intracoronary versus intravenous administration of these drugs and evaluates trials comparing different treatment strategies. Mechanical thrombectomy devices and a combined pharmacologic and mechanical approach are also reviewed.
This document discusses catecholaminergic polymorphic ventricular tachycardia (CPVT), a condition characterized by adrenergically mediated polymorphic ventricular arrhythmias without structural heart disease. It has a prevalence of 1 in 10,000 and mortality of up to 50% before age 20 if untreated. The gold standard for diagnosis is exercise stress testing showing exercise-induced bidirectional or polymorphic ventricular tachycardia. Treatment involves lifestyle changes, beta-blockers, flecainide, and an ICD for those with cardiac arrest or recurrent arrhythmias despite medical therapy. Genetic testing identifies mutations in RYR2 or CASQ2 genes in the majority of cases.
Ischaemic cardiomyopathy revascularisation how when and whycardiositeindia
This document discusses ischemic cardiomyopathy and revascularization. It begins with an overview of ischemic cardiomyopathy and discusses factors that contribute to left ventricular remodeling and heart failure progression. It then reviews data from studies such as the Duke CVD Data Bank and STITCH trial on the outcomes of coronary artery bypass grafting versus medical therapy for patients with ischemic cardiomyopathy. The document discusses the role of myocardial viability and hibernation in identifying patients most likely to benefit from revascularization. It reviews various modalities for assessing myocardial viability and hibernation such as cardiac MRI, PET, and echocardiography. Overall, the document provides an overview of ischemic cardiomyopathy and the evidence regarding revascularization outcomes based on viability assessment.
LCZ696 was more effective than enalapril in reducing the risks of CV death and HF hospitalization, CV death, HF hospitalization, and all-cause mortality in patients with heart failure with reduced ejection fraction. LCZ696 also provided incremental improvements in symptoms and physical limitations. LCZ696 was better tolerated than enalapril with lower rates of symptomatic hypotension, hyperkalemia, renal impairment, and cough.
Furosemide with matched hydration using the RenalGuard System was found to decrease the incidence of contrast-induced acute kidney injury (CI-AKI) compared to control treatments in patients undergoing interventional procedures. The RenalGuard System delivers intravenous fluids matched to urine output with hydration, furosemide, and continuous monitoring to maintain urine output over 300 ml/hr. A meta-analysis found the RenalGuard System reduced CI-AKI and need for renal replacement therapy with no increase in adverse events. However, more randomized trials are still needed to further evaluate the safety of the RenalGuard System.
Journal club multitarget therapy lupus nephritis maintenance chaken CHAKEN MANIYAN
Multitarget therapy of tacrolimus, mycophenolate mofetil and steroids achieved a 45.9% complete remission rate in induction treatment of lupus nephritis. This study assessed the efficacy of continuing multitarget therapy versus switching to azathioprine as maintenance treatment over 18 months. The cumulative renal relapse rate was lower in the multitarget group at 5.47% compared to 7.62% in the azathioprine group. More patients in the multitarget group maintained complete remission during maintenance treatment with no significant differences in safety profiles between the groups.
This document provides an overview of pulse oximetry and the oxyhemoglobin dissociation curve. It defines a pulse oximeter, describes how it works by measuring oxygenated and deoxygenated hemoglobin using light wavelengths, and notes that a normal oxygen saturation level is above 95%. The document also discusses the oxyhemoglobin dissociation curve and how shifts can occur, changing the relationship between oxygen in the blood and hemoglobin saturation. Common uses of pulse oximetry and potential limitations/interferences are outlined.
This document summarizes a study on using the dispersion width parameter (α in the Cole equation) measured through bioimpedance to monitor changes in living tissues. Through computer simulations and experiments on rat kidneys during cold preservation, the study finds:
1) The dispersion width could be determined by the morphology of the extra-cellular spaces.
2) Experiments show it is the only parameter able to detect conditions like warm ischemia prior to cold preservation or the effect of a drug disrupting the cytoskeleton.
3) The bioimpedance is useful not only for monitoring intra/extra-cellular volume but also for detecting tissue structural alterations, thanks to the dispersion width parameter.
Photoplethysmographic assessment of pulse wave reflection: Blunted response to mellitus -adrenergic vasodilation in type II diabetes 2
endothelium-dependent beta
This study examined how extracellular dopamine (DA) levels in the striatum are regulated during anoxia in the anoxia-tolerant turtle Trachemys scripta. The main findings were:
1) Basal extracellular DA levels in the normoxic turtle striatum were similar to levels in mammals. DA levels increased when DA reuptake was blocked but not during anoxia.
2) Inhibition of sodium-potassium ATPase increased extracellular DA levels in normoxic and anoxic turtles, indicating ion gradients are important for maintaining low DA.
3) Blocking DA reuptake during anoxia increased extracellular DA levels, showing uptake mechanisms function during anox
The study analyzed arterial pulse recordings from 1,005 subjects aged 2-91 years using a new tonometry technique. Three main findings were observed with increasing age: (1) pulse amplitude increased in all artery sites, (2) diastolic decay steepened and diastolic waves diminished, (3) carotid pulses showed a merging of two systolic peaks. These changes reflect increased arterial stiffness and earlier wave reflections with age.
Cerebral Perfusion Response
to Successful Treatment of
Depression With Different
Serotoninergic Agents with antidepressant therapy have been reported in a number of studies.2–4 In contrast, decreases in the ventral anterior cingulate blood flow were found in response to desipramine,5 electroshock therapy,6 and flu-7
This document describes several physiologic data collection products from LD Products including a galvanic skin response device, body composition analyzer, and photoelectrical plethysmography device. It also discusses software for data interpretation and management, as well as telemedicine services. The ES Complex combines multiple technologies into a single device for measuring parameters like heart rate, blood oxygen levels, pulse analysis, and body composition. It enables early diagnosis and management of conditions like metabolic syndrome, diabetes, and cardiovascular disease through non-invasive screening tests.
EIS Technology: bioimpedance chronoamperometry in adjunct to screen the prost...ES-Teck India
Through the 6 tactile electrodes, a weak DC current is sending alternatively between 2 electrodes with a sequence and the EIS system is recording the electrical conductance of 11 pathways of the human body.
1. Pulse wave analysis in historical times was an important part of medical examination but fell out of favor with the introduction of the cuff sphygmomanometer.
2. Modern pulse wave analysis is regaining favor as limitations of the cuff are recognized. Accurate recording and analysis of the arterial pulse is now possible through high-fidelity tonometry and understanding of arterial hemodynamics.
3. Analysis of pulse waveforms can provide clinically important information about ventricular-vascular interaction and disease states like hypertension that was previously only available through invasive methods.
Noninvasive Cardiac Output Estimation Using a Novel
Photoplethysmogram Index
31st Annual International Conference of the IEEE EMBS Minneapolis, Minnesota, USA, September 2-6, 2009
Summary of clinical investigations es teck complex systemES-Teck India
Summary of the clinical investigations E.S.Teck Complex March, 20, 2010
Summary of Clinical Investigations ES Teck Complex system EIS System in adjunct to Treatments’ monitoring and to diagnosis with the conventional methods
Bioimpedance describes the passive electrical properties of biological materials and serves as an indirect transdu-
cing mechanism for physiological events, often in cases
where no specific transducer for that event exists. It is an
elegantly simple technique that requires only the applica-
tion of two or more electrodes. electrodes are equal, it is called a bipolar lead, in contrast
to a monopolar lead. With 3-(tetrapolar) or 4-(quadropo-
lar) electrode systems, separate current carrying and
signal pick-up electrodes exist. The impedance is then
transfer impedance (12): The signal is not picked up from
Comparison of Invasive vs Noninvasive Pulse Wave Indices in Detection of Signifi cant Coronary Artery Disease: Can We Use Noninvasive Pulse Wave Indices as Screening Test
This study investigated syncope recurrence in patients with a type 2A cardioinhibitory response to head up tilt testing without a significant asystolic pause. 72 patients underwent either an electrophysiological study or were observed without intervention. Those who underwent the study and received ablation or device implantation had a lower rate of syncope recurrence during the 1 year follow-up compared to those who did not receive an intervention. The electrophysiological study result was the only factor that predicted syncope recurrence, suggesting it may help identify underlying arrhythmias contributing to syncope in these patients.
Caso clínico líquidos en neuroanestesiaSocundianeste
This document summarizes the case of a 23-year-old male patient who presented with headaches, visual symptoms, and an intraventricular lesion. The patient underwent neurosurgery to remove a meningioma. Intraoperatively, the patient was closely monitored and received various anesthetics, fluids, and blood products. Post-operatively, the patient had an excellent recovery without neurological deficits. The document also discusses the use of albumin in neurosurgical patients and compares outcomes of albumin versus saline resuscitation in patients with traumatic brain injury based on a previous clinical trial.
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 the prognostic value of perioperative near-infrared spectroscopy (NIRS) monitoring of cerebral and renal oxygen saturation in 41 neonates and infants undergoing congenital heart surgery with cardiopulmonary bypass. NIRS and other physiological parameters were measured at multiple time points. The results showed that cerebral and renal NIRS values below certain thresholds correlated with adverse outcomes like death or need for ECMO support. Cerebral and renal NIRS also correlated with longer ICU stays. Additionally, 10 minutes of modified ultrafiltration at the end of bypass did not adversely affect NIRS readings in the brain or kidneys.
Wet cupping therapy was applied to 5 points on the back of 40 healthy participants. Electrocardiography recordings were taken before and after to analyze heart rate variability (HRV), a measure of sympathovagal balance. All HRV parameters, including SDNN, SDANN, RMSSD, pNN50, LF, and HF, increased after cupping therapy compared to before, indicating cupping restored sympathovagal balance. This is the first study to show in humans that cupping therapy may have cardioprotective effects by stimulating the peripheral nervous system.
This document discusses hyperkalemia (high potassium levels), including its causes, effects on the heart, diagnosis, and treatment. It describes a case report of a 69-year-old woman who experienced hyperkalemia after dialysis. Her symptoms included abdominal pain, fatigue, and arrhythmia. Treatment involved calcium, insulin, glucose, and emergent dialysis to lower her potassium level. The document then provides details on potassium regulation in the body, effects of high potassium on heart function, electrocardiogram changes seen with hyperkalemia, common causes, and approaches for treating acute hyperkalemia including membrane stabilization, promoting potassium influx, and potassium removal methods like dialysis or sodium polystyrene sulfonate.
This study examined urinary levels of C-type natriuretic peptide (CNP) in patients with acute decompensated heart failure (ADHF) and healthy controls. The study found that ADHF patients had higher levels of three CNP molecular forms (CNP22, CNP53, and NT-CNP53) in their urine than controls. Higher urinary levels of NT-CNP53 in ADHF patients predicted higher mortality and rehospitalization rates. NT-CNP53 was a better predictor of outcomes than other urinary biomarkers of kidney injury and provided additional predictive value when combined with plasma levels of NT-proBNP. The findings suggest urinary CNP levels have clinical utility as biomarkers
Utility value of tilt table testing in evaluationUday Prashant
I had presented in CARE Highlights session and book is being published on this topic by LAMBERT publications, Germany
http://www.google.co.in/url?sa=t&rct=j&q=&esrc=s&frm=1&source=web&cd=1&cad=rja&ved=0CCoQFjAA&url=http%3A%2F%2Fwww.amazon.in%2FEvaluation-Unexplained-Syncope-Young-Adults%2Fdp%2F3843373175&ei=lzVtUvbtCIfSrQemkYDwCg&usg=AFQjCNEK_NmIVC5j5LcLSr2hKbYFwMmRuw&sig2=okLwwgOdFiPgw4GPk7mugQ&bvm=bv.55123115,d.bmk
1. Basic monitoring standards established by anesthesia societies require monitoring of circulation, ventilation, and oxygenation including ECG, blood pressure, capnography, and pulse oximetry.
2. Pulse oximetry uses light absorption to measure oxygen saturation and heart rate while capnography monitors expired carbon dioxide.
3. Invasive arterial blood pressure monitoring provides direct measurement but risks include hematoma and nerve damage.
ARVC and flecainide case report[EI] Jim.docx.pdfJim Dowling
This case report describes a patient diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC) due to a mutation in the titin gene. Initial treatment with beta-blockers for exercise-induced ventricular arrhythmias was ineffective. Treatment with flecainide dramatically improved the patient's symptoms. After 6 years of flecainide treatment, the patient can engage in low-intensity activities without issues. The report highlights the potential efficacy of flecainide for ARVC patients with exercise-induced arrhythmias and preserved heart function.
This document describes a study that used coded harmonic angio ultrasound with microbubble contrast agents to evaluate renal perfusion abnormalities. The study found that CHA ultrasound can effectively depict the enhancement patterns of various renal lesions and abnormalities compared to dynamic CT. For renal cell carcinomas, the most common enhancement pattern seen on CHA ultrasound was heterogeneous enhancement. Transitional cell carcinomas predominantly showed peripheral enhancement. Patients with acute pyelonephritis or renal trauma demonstrated focal perfusion defects not visible on pre-contrast images. The study concludes that CHA ultrasound with microbubble contrast is effective for evaluating tumor vascularity and other renal perfusion abnormalities.
The document summarizes a study comparing outcomes of patients who underwent aortic arch surgery using antegrade cerebral perfusion (ACP) versus without ACP. The study found significantly lower rates of postoperative stroke (2% vs 13%) and better 3-year survival (93% vs 78%) in the ACP group. Multivariate analysis confirmed ACP was associated with reduced stroke risk and improved long-term survival. The results suggest ACP provides neuroprotective and survival advantages over surgery without ACP for aortic arch pathology requiring prolonged repair periods.
Use of Capnograph in Breathlessness Patientsnhliza
This is a research topic carried out in the Emergency Department and the abstract was presented at the International Conference In Emergency Medicine in SanFrancisco April 2008
Cerebral oximetry as a real time monitoring tool to assess qualityEmeka Onuorah
This study evaluated the use of near-infrared spectroscopy to monitor regional cerebral oxygen saturation (rSO2) during in-hospital cardiac resuscitation and post-cardiac arrest care. Higher rSO2 levels at the start of resuscitation and during resuscitation were associated with achieving return of spontaneous circulation, but rSO2 was not predictive of survival to discharge or good neurological outcomes. While rSO2 may reflect the quality of cardiopulmonary resuscitation, larger studies are still needed to determine if rSO2 monitoring can be used to improve clinical outcomes after cardiac arrest.
This study evaluated the feasibility of transthoracic echocardiography (TTE) for assessing cardiac function in 76 patients with septic shock. TTE was able to determine left ventricular systolic function in 90% of patients, right ventricular function in 99%, and left ventricular diastolic function in 73%. Diastolic dysfunction was present in 50% of patients. Factors like obesity, mechanical ventilation, age, and illness severity did not impact the ability of TTE to evaluate cardiac function. TTE is therefore a reliable tool for comprehensive cardiac assessment, including diastolic function, in critically ill septic shock patients.
This study compared the effects of levosimendan, dobutamine, and vasodilator therapy on ongoing myocardial injury in patients with acute decompensated heart failure. The study found that while all treatments were associated with decreases in cardiac troponin I levels and improvements in hemodynamic and functional indicators, levosimendan treatment showed the most pronounced improvements, especially in left ventricular ejection fraction and systolic pulmonary artery pressure. However, none of the treatments significantly reduced cardiac troponin I levels compared to each other. The study demonstrated beneficial effects of short-term use of levosimendan, dobutamine, and nitroglycerin on ongoing myocardial injury in acute decompensated heart failure.
The study to measure the level of serum annexin V in patients with renal hype...inventionjournals
ABSTRACT : Renovascular hypertension reflects the causal relation between anatomically evident arterial occlusive disease and elevated blood pressure. The coexistence of renal arterial vascular disease and hypertension roughly defines this type of nonessential hypertension. The aim of this study was to measure the level of serum Anti-Annexin V antibodies in patients with renal hypertension. Methods. This study was conducted on 115 patients, diagnosed with renal hypertension and hypertension. Informed consents were obtained from the patients and the study was approved by the Kharkiv National Medical University ethics committee. Ten healthy age and sex matched volunteers were included as a control group. All patients and controls were subjected to the following full history taking and thorough clinical examination. Routine laboratory testing included a complete blood count, and erythrocyte sedimentation rate (ESR) and kidney function tests (blood urea nitrogen and serum creatinine). Immunological tests for antinuclear antibody (ANA) and anticentromere antibodies (ACA) was performed by the indirect immunofluorescence technique. AntiScl-70 (anti-topoisomerase antibodies) and anticardiolipin antibodies (ACA: IgG and IgM) were tested using the ELISA technique. The anti-annexin V antibodies titre used the ZYMUTEST anti-Annexin IgG ELISA kit. [Hyphen-BioMed, France.]: to measure the IgG isotype of auto-antibodies to annexin V in human serum. Results. Anti-annexin V antibodies were present in 75% of patients (mean 83.46 ± 22.44 AU/mL) vs. 0% in the controls (mean 3.94 ± 4.5 AU/mL). Comparison between patients and controls as regards levels of anti-annexin V showed a highly significant difference (P < 0.001). Furthermore, correlation of anti-annexin V titres with the disease activity score in the patient group showed a statistically significant positive correlation (r = 0.51, P < 0.05).In addition, the anti-annexin V antibody titres in this study showed a highly significant positive correlation with ACL antibodies (r = 0.74, P < 0.001). Patients with antiphospholipid syndrome (APS) have been known to have a higher frequency of anti-annexin V antibodies, and thrombotic events have been reported more frequently in patients with positive anti-annexin V antibodies. Furthermore, inhibition of annexin V binding to negatively charged phospholipids may be an additional pathogenic mechanism of APS.
Aim: To study the value of BNP as a screening tool to identify silent ischemia and diastolic dysfunction in asymptomatic type II
diabetic patients.
Objectives: The objective of the study is how far BNP value will be useful in early detection of LV dysfunction and ischemia without subjecting the patient to treadmill test and ECHO, as both are even though specific but not sensitive. Our effort is to identify a simple blood test which is highly sensitive in identifying them.
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...iosrphr_editor
This study investigated the effects of oral clonidine premedication on hemodynamic changes during laparoscopic cholecystectomy. 100 patients were randomly assigned to receive either oral clonidine 150 micrograms or ranitidine 150 mg 90 minutes before surgery. Heart rate, blood pressure, and the need for antihypertensive treatment were significantly lower in the clonidine group during and after surgery. Postoperative nausea, vomiting, shivering, pain, and sedation were also reduced with clonidine premedication. The results suggest that oral clonidine can provide hemodynamic stability and reduce postoperative complications for patients undergoing laparoscopic cholecystectomy.
This document discusses goal directed fluid therapy and fluid management in the perioperative period. It begins by introducing the importance of intravenous fluid therapy and issues related to both excess and restrictive fluid administration. It then discusses various fluid monitoring techniques including static parameters measured by pulmonary artery catheters, minimally invasive monitors like LiDCO and pulse contour analysis devices, dynamic parameters like stroke volume variation, and echocardiography. The document also addresses fluid responsiveness, factors influencing venous return and the Frank-Starling relationship, and the high incidence of non-responders to fluid challenges.
Similar to Arterioscler thromb vasc_biol_22_147 (20)
EIS technology : bioimpedance application in selective serotonin reuptakeES-Teck India
Through the 6 tactile electrodes, a weak DC current is sending alternatively between 2 electrodes with a sequence and the EIS-GS system is recording the electrical conductance of 11 pathways of the human body.
The document summarizes a research article that examines the relationship between parameters derived from the second derivative of finger photoplethysmogram (PPG) signals and pulse wave velocity (PWV), a measure of arterial stiffness. The study found low but significant correlations between the PPG parameters and PWV. While the measures provide related information on arterial properties, they are not equivalent since PWV reflects aortic stiffness passive effects on pressure, while PPG parameters depend on both central and peripheral effects including ventricular ejection. The relationship between PPG and PWV is complex due to different underlying mechanisms assessed and potential sources of error in the non-invasive techniques.
Guidelines heart rate_variability_ft_1996[1]ES-Teck India
Guidelines
Heart rate variability
Standards of measurement, physiological interpretation, and
clinical use
Task Force of The European Society of Cardiology and The North American
Society of Pacing and Electrophysiology (Membership of the Task Force listed in
the Appendix)
Hypertension:Volume 32(2)August 1998pp 365-370
Assessment of Vasoactive Agents and Vascular Aging by the Second Derivative of
Photoplethysmogram Waveform
[Third Workshop On Structure And Function Of Large Arteries: Part Ii]
The document discusses pulse oximetry and oxygen saturation.
[1] A pulse oximeter uses light to determine the percentage of hemoglobin in blood that is saturated with oxygen (SpO2). It also measures pulse rate.
[2] Oxygen is brought into the lungs and transfers to blood in lung capillaries. It is transported throughout the body bound to hemoglobin in red blood cells.
[3] Oxygen saturation measured by a pulse oximeter (SpO2) indicates if sufficient oxygen is being supplied to tissues. Monitoring SpO2 can help assess disease severity and determine need for treatment.
This study examined the effects of intracisternally injected serotonin on cerebral blood flow and systemic pressure in cats during winter and summer months. The researchers found that serotonin produced decreases in cerebral blood flow and systemic pressure lasting 60 to 180 minutes after injection. The decreases in blood flow were significantly greater in winter than summer, but decreases in systemic pressure were not different between seasons. Cats exposed to 3 days of darkness before serotonin injection experienced greater decreases in blood flow compared to light-exposed cats, while systemic pressure changes were similar. The findings suggest the photoperiod may affect the sensitivity of cerebral vessels to serotonin in cats.
The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment
of the risk/benefit profile. Nutritional Journal
Effects of dopamine on
posttraumatic cerebral blood flow, brain edema, and cerebrospinal fluid
glutamate and hypoxanthine concentrations. Critical Care Medicine,
28(12):3792-3798.
Correlation between organ dysfunctions and vertebral displacementsES-Teck India
Correlation between organ dysfunctions and
vertebral displacements
In a prospective study a comparison was made between a control group (a group of
patients with displaced vertebrae but without organic complaints) and different groups of
patients who were not only characterised by displaced vertebrae but also by various organ
dysfunctions. Six groups of patients were differentiated: patients with gastric complaints,
intestinal complaints, heart conditions, asthma, hyperventilation and migraine. Of these
seven groups curves have been made to show the mean number of abnormalities per
vertebra. The curves of patients with an organic complaint were compared with the curves of patients without organic complaints. The differences, which are pronounced, are discussed in this article.
The document discusses the dielectric properties of biological tissues. It notes that tissues typically display high dielectric constants at low frequencies that decrease in distinct steps as the excitation frequency increases, due to different polarization mechanisms. The document outlines three main dispersions - alpha, beta, and gamma - observed in tissue, which correspond to low, radio, and microwave frequencies respectively. Each dispersion is caused by a different mechanism, such as cell membranes or tissue water. The dielectric properties provide information about tissue composition and structure.
This thesis examines the use of electrical bioimpedance for cerebral monitoring by investigating the biophysical basis and effects of hypoxic/ischemic brain damage on tissue impedance, developing instrumentation for impedance measurements, and analyzing sensitivity maps to determine the clinical feasibility of the method.
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
Travel Clinic Cardiff offers comprehensive travel health services, including vaccinations, travel advice, and preventive care for international travelers. Our expert team ensures you are well-prepared and protected for your journey, providing personalized consultations tailored to your destination. Conveniently located in Cardiff, we help you travel with confidence and peace of mind. Visit us: www.nxhealthcare.co.uk
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
DECLARATION OF HELSINKI - History and principlesanaghabharat01
This SlideShare presentation provides a comprehensive overview of the Declaration of Helsinki, a foundational document outlining ethical guidelines for conducting medical research involving human subjects.
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The skin is the largest organ and its health plays a vital role among the other sense organs. The skin concerns like acne breakout, psoriasis, or anything similar along the lines, finding a qualified and experienced dermatologist becomes paramount.
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2. 148 Arterioscler Thromb Vasc Biol. January 2002
determine whether albuterol acts via the L-arginine–NO Protocol
pathway; to apply the technique to a large cohort of healthy Subjects were studied in the morning after an overnight fast. Subjects
controls and hypercholesterolemic subjects, the latter of with an elevated blood pressure at screening ( 160/100 mm Hg),
diabetes mellitus, or a clinical history of cardiovascular disease were
whom are known to exhibit endothelial dysfunction2; and excluded, as were individuals receiving medication. Studies were
then to compare the technique with the “gold standard” of conducted in a double-blind fashion (where appropriate) in a quiet,
forearm venous occlusion plethysmography.3 temperature-controlled room (22 2°C). All hemodynamic record-
ings were made in duplicate. Three sets of recordings were made
during a 45-minute period of supine rest, and the last was taken as a
Methods baseline. Recordings were made 3, 5, 10, 15, and 20 minutes after
All studies were conducted at the Clinical Pharmacology Unit, NTG administration and 5, 10, 15, and 20 minutes after albuterol or
University of Edinburgh; the Clinical Pharmacology Unit, University aerosol placebo. Pilot studies had confirmed that 20 minutes was
of Cambridge, and the Wales Heart Research Institute, University of sufficient for the hemodynamic changes after NTG to return to
Wales, Cardiff. Healthy subjects were enrolled from community baseline but that a longer period was required for albuterol. There-
databases of volunteers, and patients were recruited from cardiovas- fore, NTG was always administered first, followed by albuterol 25
cular risk clinics and family practices local to all institutions. minutes later.
Approval for all studies was obtained from the respective local
research ethics committees, and informed consent was obtained from Study 1: Repeatability
each participant. Thirteen healthy subjects (11 male) were studied on 3 occasions,
separated by 1 week. After baseline recordings of heart rate, blood
pressure, CI, and radial artery waveforms were made, subjects
Hemodynamics received sublingual NTG. This was followed by albuterol (on 2
Blood pressure was recorded in duplicate in the dominant arm by occasions) or matching placebo (once) in random order. Blood was
using a validated oscillometric technique (HEM-705CP, Omron taken for estimation of plasma albuterol at baseline and at 5-minute
Corp). Cardiac index (CI) was assessed noninvasively by using a intervals thereafter.
validated12 transthoracic electrical bioimpedance technique (BoMed
NCCOM3-R7), and peripheral vascular resistance (PVR) was calcu- Study 2: Inhibition of NO Synthase
lated as mean arterial pressure (MAP) divided by CI. Twelve healthy males were studied on 6 occasions, separated by 1
Radial artery waveforms were recorded with a high-fidelity week. An 18-gauge cannula was sited in the nondominant arm and
micromanometer (SPC-301, Millar Instruments) from the wrist of saline infused for 30 minutes. After baseline recordings of heart rate,
the dominant arm. PWA (SCOR 6.1, PWV) was then used to blood pressure, CI, and radial artery waveforms were made,
generate a corresponding central waveform by using a validated LNMMA was then infused for 15 minutes alone, on 3 occasions,
transfer function,13–15 as previously described.16 From this, augmen- followed by administration of NTG, albuterol, or matching aerosol
tation index (AIx) and heart rate were determined by using the placebo. On the other 3 visits, NE was infused in place of LNMMA.
integral software. AIx, a measure of systemic arterial stiffness,9 was The order of administration of all drugs was fully randomized.
calculated as the difference between the second and first systolic
peaks, expressed as a percentage of the pulse pressure. Study 3: Hypercholesterolemia
Twenty-seven hypercholesterolemic subjects (total cholesterol
6.0 mmol · L 1) and 27 matched normocholesterolemics
Venous Occlusion Plethysmography ( 6.0 mmol · L 1) were studied. Heart rate, blood pressure, and
The brachial artery of the nondominant arm was cannulated with a radial artery waveforms were assessed at baseline and after NTG and
27-gauge steel needle (Coopers Needle Works) under local anesthe- albuterol administration. Twenty minutes after albuterol was given,
sia, and blood flow was measured simultaneously in both arms by blood was taken for determination of cholesterol (total, LDL, and
venous occlusion plethysmography, with temperature-compensated, HDL), glucose, and albuterol concentrations.
indium/gallium-in–silicone elastomer strain gauges, as previously
described.17 Blood flows were recorded during the final 3 minutes of Study 4: Comparison With Venous Occlusion Plethysmography
each infusion period, and the mean of the final 5 measurements was Twenty-seven subjects with a range of serum cholesterol values (3 to
used for analysis. 8.6 mmol · L 1; 12 subjects 6.0) but no other cardiovascular risk
factors were studied on a single occasion. Endothelial function was
Plasma Albuterol Assay first assessed invasively by venous occlusion plethysmography
Venous blood (10 mL) was taken from the antecubital fossa into coupled with an intra-arterial infusion of SNP and ACh (after 30
minutes of saline infusion and a 20-minute washout between drugs).
lithium-heparin tubes and centrifuged immediately at 4°C (2000g for
After a further 30 minutes, endothelial function was then assessed by
10 minutes). The plasma was then removed and stored at 80°C for
PWA coupled with administration of NTG and albuterol.
later analysis by a chiral liquid chromatography/tandem mass spec-
trometry technique.18 The lower limit of detection for the assay was
0.05 ng · mL 1, and the coefficient of variation was 10%. Data Analysis
The response to albuterol, placebo, or NTG was defined as the
maximum change in each parameter after drug administration (an
Drugs a priori summary measure). Forearm blood flow was calculated as
Albuterol (Allen and Hanbury’s) was given by inhalation with a mL · min 1 · 100 mL 1 tissue, and the ratio of blood flow in the
spacer device (2 200 g). A 500- g tablet of NTG (Cox) was infused to the noninfused arm was used to reduce blood flow
placed under the tongue for 3 minutes and then removed. Norepi- variability in response to extraneous stimuli such as temperature
nephrine (NE, Abbott Laboratories) and NG-monomethyl-L-arginine fluctuations.21 Again, the maximum responses to albuterol and to
(LNMMA, Clinalfa) were prepared aseptically with 0.9% saline as a ACh were used as a priori summary measures. Data were analyzed
diluent and infused intravenously at 1 mL · min 1. LNMMA was by SPSS software (version 9.0) and unpaired or paired, 2-tailed
given as a bolus of 3 mg · kg 1 (5 minutes) and then continuously at Student’s t tests or ANOVA, as appropriate. Multiple regression
3 mg · kg 1 · h 1 for 45 min. NE was infused at 50 ng · kg 1 · h 1 for analysis was conducted by using the “enter method.” Repeatability
45 min as a control constrictor; the dose was chosen from pilot was assessed by constructing Bland-Altman plots and reported as the
studies and published literature to produce an elevation of MAP and mean SD of the differences between samples.22 All values repre-
AIx similar to that effected by LNMMA.19,20 SNP (David Bull sent mean SD, and a P value 0.05 was considered significant. All
Laboratories) at 3 and 10 g · min 1 and ACh (Novartis) at 7.5 and changes cited represent absolute differences, rather than percentage
15 g · min 1 were infused intra-arterially, each for 6 minutes. changes.
3. Wilkinson et al Assessment of Endothelial Function 149
TABLE 1. Hemodynamic Changes in Study 1
Albuterol (1) NTG (1) Albuterol (2) NTG (2) Placebo NTG (3)
AIx, % 9.3 3.8‡ 12.8 4.4‡ 11.6 3.8‡ 13.0 7.0† 0.2 5.4 11.1 5.9‡
MAP, mm Hg 1 3 2 8 1 4 3 5 1 7 2 4
1 2
CI, L min m 0.5 0.6*§ 0.1 0.3 0.7 0.6* 0.2 0.4 0 0.3 0.2 0.2
PVR, AU 2.9 4.7* 0.2 3.4 1.0 4.3* 0.7 4.6 0.6 4.8 0.3 2.7
1
HR, beats min 3 5† 6 7* 5 6* 1 6 0 5 0 4
Changes in AIx, MAP, CI, PVR, and heart rate (HR) after albuterol, matching placebo, or NTG. Numbers in parentheses refer to visit
number. AU indicates arbitrary units.
Values represent means SD, and significant changes from baseline are indicated by *P 0.0.5, †P 0.01, ‡P 0.001. Significant
differences in the response between albuterol and placebo are indicated in column by §P 0.05, P 0.001; n 13.
Results or albuterol in either group. AIx fell significantly after adminis-
tration of albuterol, but the response was significantly reduced in
Study 1
The mean age of the subjects was 37 years (range, 25 to 56). hypercholesterolemics compared with controls ( 7.4 5.7% vs
There were no significant differences in baseline values 11.9 7.7%, respectively; P 0.02). Despite this disparity, the
between the 3 visits. The hemodynamic changes are shown in time to maximum change (12 3 vs 11 3 minutes, P 0.2) and
Table 1. Only AIx (P 0.001) and CI (P 0.01) changed peak plasma albuterol concentrations (1.2 0.6 vs 1.1 0.5 ng ·
significantly after albuterol. There was no difference in the mL 1, P 0.5) were similar in both groups. Moreover, the
mean response to albuterol compared with NTG for any maximum change in AIx after NTG ( 14.8 8.4% vs
parameter except CI (P 0.02). The response to albuterol or 10.2 9.0%, P 0.1) did not differ significantly.
NTG did not differ between visits. The mean difference in the To investigate further the factors influencing the response to
AIx response between visits was 2.3 3.0% and albuterol, a multiple linear regression model was constructed,
0.2 6.5% for albuterol and NTG, respectively. with change in AIx as the dependent variable. Age, sex, weight,
Plasma albuterol was below the level of detection at smoking status, baseline MAP and AIx, LDL and HDL choles-
baseline and after administration of placebo. Plasma albuterol terol, triglycerides, glucose, and change in MAP and heart rate
increased after administration of the active drug (P 0.001 on were entered into the model. Variables with a significance
both occasions, Figure 1), and there was no difference in the 0.25 were then removed and the analysis repeated. The final
peak albuterol concentration between visits (mean difference model (Table 4) explained 60% of the variability in the
of 0.12 0.55 ng · mL 1, P 0.9). response to albuterol. Change in AIx was negatively associated
with plasma LDL and glucose and positively correlated with
Study 2 plasma albuterol concentration and fall in heart rate.
The mean age of the subjects was 32 years (range, 22 to 52).
There were no significant differences in baseline values Study 4
across the 6 visits. Hemodynamic changes are summarized in Resting forearm blood flow did not differ between the 2 arms,
Table 2. The effects of NE and LNMMA did not differ and there was no change in blood flow in the noninfused arm
significantly between visits. Both drugs had similar effects on during the study (data not shown). As expected, blood flow
AIx, MAP, and heart rate, but there was a greater change in increased significantly during infusion of SNP and ACh
CI (P 0.001) and PVR (P 0.001) with LNMMA. The (P 0.001 for both, ANOVA). However, the response to ACh
responses to NTG and placebo with LNMMA did not differ (7.5 g · min 1: 1.6 1.0 vs 3.4 1.0 mL · min 1 · 100 mL 1,
significantly from those during coinfusion of NE. However, P 0.003; and 15.0 g · min 1: 2.0 0.3 vs 5.8 0.3 mL ·
albuterol had less effect on AIx during infusion of LNMMA min 1 · 100 mL 1, P 0.04) but not to SNP was reduced in
(P 0.02, Figure 2A), despite causing a greater reduction in subjects with a cholesterol level 6.0 mmol · L 1. NTG and
MAP (P 0.001) and PVR (P 0.001). albuterol both significantly reduced AIx (P 0.001), and the
response to albuterol (r 0.5, P 0.02) was related to serum
Study 3 cholesterol. There was a significant, linear relationship be-
The baseline characteristics of the subjects are given in Table 3.
tween the absolute change in AIx after albuterol and the
There was no significant change in MAP or heart rate after NTG
change in the forearm blood flow ratio during infusion of
ACh at 15 g · min 1 (Figure 2B). There was no relationship
between the response to SNP and to NTG.
Discussion
This study describes the effects of albuterol and NTG on the
aortic pressure waveform. AIx, a quantitative index of systemic
arterial stiffness,9 was calculated from aortic waveforms gener-
ated by PWA.10 Our main novel findings are that albuterol and
NTG produce qualitatively and quantitatively similar and repeat-
able effects on AIx, that the effect of albuterol but not of NTG
Figure 1. Changes in plasma albuterol concentration after visits is inhibited by LNMMA and reduced in hypercholesterolemic
1 ( ) and 2 (▫); n 13. subjects, and that the response to albuterol is correlated with the
4. 150 Arterioscler Thromb Vasc Biol. January 2002
TABLE 2. Hemodynamic Changes in Study 2
NE LNMMA
NE Albuterol NTG Placebo LNMMA Albuterol NTG Placebo
AIx, % 10.7 10.5‡ 9.8 5.5‡ 12.5 11.1‡ 0.4 6.2 6.1 9.7‡ 4.7 2.7‡ 13.4 2.4‡ 1.2 5.5
MAP, mm Hg 7 8† 1 3‡ 5 4‡ 4 6* 6 6‡ 4 6* 4 4* 2 6
1 2
CI, L min m 0.1 0.4* 0.8 0.4‡ 0.1 0.4 0.1 0.3 0.6 0.6‡ 0.6 0.4‡ 0.1 0.2 0.1 0.3
PVR, AU 3.2 4.3† 2.5 5.8† 1.1 3.1 0.5 2.2 7.3 4.8‡ 6.4 4.0‡ 2.5 3.3* 1.6 3.4
1
HR, beats min 5 6† 9 5‡ 4 4* 2 7 6 6‡ 5 4‡ 2 4 1 6
Changes (means SD) in AIx, MAP, CI, PVR, and heart rate (HR) during study 2. NE or LNMMA was infused, and then albuterol, matching placebo, or NTG was
administered. AU indicates arbitrary unit.
*P 0.0.5, †P 0.01, ‡P 0.001.
effect of ACh in the forearm vascular bed. These data indicate lium-dependent NO dilators has not been reported. Neverthe-
that the effect of albuterol is, in part, NO and endothelium less, comparable changes in the volume waveform after
dependent and are constistent with the presence of endothelial infusion of ACh into rabbits30 and of NTG and albuterol into
dysfunction in hypercholesterolemic subjects. Moreover, they humans11 have been described. However, unlike Chowienc-
suggest that PWA and administration of albuterol and NTG zyk et al11 and relevant to wider application of the present
provide a simple, reliable, noninvasive method for assessing technique, we included a suitable placebo and showed that the
endothelial function, as we and others have previously responses to albuterol and NTG are repeatable. We also
hypothesized.23,24 measured plasma albuterol concentrations, which were rela-
As expected, inhalation of albuterol at the dose used tively stable between 5 and 20 minutes (Figure 1). This
reduced AIx without any accompanying alteration in heart pharmacokinetic profile is in keeping with the pharmacody-
rate or MAP, compared with placebo, which is important namic response to albuterol. Peak plasma levels did not differ
because AIx is influenced by both.20,25 The magnitude of the significantly between visits, confirming that inhalation of
response to both drugs was comparable, and the repeatability, albuterol with a spacer device provides a repeatable method
high. Indeed, the repeatability is similar to what we previ- of drug delivery. As might be expected, the results of the
ously reported for PWA16 and to values quoted for other multiple regression analysis from study 3 (Table 4) demon-
techniques of assessing endothelial function, such as intra-ar-
strated a significant relationship between plasma albuterol
terial infusion of ACh26 and flow-mediated dilatation.27
and the maximum change in AIx. Therefore, some of the
Previous studies have shown similar changes in the arterial
variability in the response to albuterol between subjects may
pressure waveform after NTG,28,29 but the effect of endothe-
have been due to differences in drug absorption and peak
plasma concentrations. Such an effect may be important when
making comparisons between subjects groups, especially
when relatively small numbers of subjects are studied or
smokers are included, when plasma albuterol values may
improve the reliability of data interpretation.
To investigate the NO dependence of albuterol, we infused
LNMMA, a specific substrate-analogue inhibitor of NO
synthase. However, because systemic LNMMA infusion
TABLE 3. Subject Characteristics in Study 3
Hyper- Significance,
Controls cholesterolemics P
Age, y 47 11 48 11 0.8
Male/female, n/n 21/6 22/5 1.0
Smokers, n 5 5 1.0
Height, m 1.73 0.06 1.68 0.09 0.3
Weight, kg 74.8 13.8 78.8 13.6 0.2
1
Cholesterol, mmol L 5.1 0.6 6.6 0.5 0.001
1
LDL, mmol L 2.9 0.8 4.5 0.9 0.001
1
HDL, mmol L 1.3 0.4 1.3 0.3 0.6
1
Triglycerides, mmol L 2.0 1.6 2.2 1.1 0.7
Figure 2. A, Effect of inhibition of NO synthase on the response Glucose, mmol L 1
5.0 0.5 5.3 1.7 0.3
to NTG, albuterol, and placebo. Changes in AIx after albuterol,
NTG, and placebo during infusion of NE ( ) and NG-monometh- MAP, mm Hg 84 9 90 12 0.04
1
yl-L-arginine ( ); n 12, *P 0.05. B, Relationship between the Heart rate, beats min 66 9 65 7 0.5
response to albuterol and ACh. Change in AIx after albuterol
AIx, % 15 7 21 9 0.04
and change in forearm blood flow (FBF) after ACh. A regression
line is shown, for which r 0.5, P 0.02, slope 9.8, n 27. Values represent means SD.
5. Wilkinson et al Assessment of Endothelial Function 151
TABLE 4. Results of the Regression Analysis for Study 3, With and with acute hyperglycemia in normal subjects.39 However,
Change in AIx After Albuterol as the Dependent Variable any relationship between insulin sensitivity and endothelial
Regression function in nondiabetic subjects is controversial.40,41 More-
Variable Units Coefficient SD P over, data concerning cardiovascular risk and plasma glucose
1 in normal subjects are divided.42 Nevertheless, glycosylated
Glucose mmol L 6.4 1.7 0.001
1
hemoglobin is positively associated with the risk of future
LDL cholesterol mmol L 2.1 0.8 0.012
coronary heart disease risk in a linear, stepwise manner,43
1
Albuterol ng mL 3.9 2.2 0.021 suggesting a continuum of risk across the glycemic range,
1
Change in heart rate beats min 0.4 0.1 0.001 which may be explained by the inverse relationship between
Smoking 3.5 2.2 0.13 endothelial function and plasma glucose in the present study.
Biochemical parameters were derived from plasma samples, and the R2 for To compare our novel methodology for noninvasive as-
the entire group was 0.61, P 0.001, n 54. sessment of endothelial function with a more established one,
we assessed endothelial function by both PWA and forearm
alters MAP and heart rate,19 we used NE as a control vasocon- blood flow in 27 individuals with a wide range of serum
strictor to produce comparable hemodynamic changes.20 As cholesterol values. As previously noted,3 we observed a
expected, but not previously reported, we observed a significant significant blunting of the vasodilator effect of ACh, but not
increase in AIx with administration of LNMMA. However, both of SNP, in subjects with a serum cholesterol value 6 mmol
drugs had similar effects on AIx, heart rate, and MAP, but the · L 1. Moreover, as in study 3, the response to albuterol but
response to albuterol was significantly attenuated by LNMMA, not to NTG was related to serum cholesterol. The main novel
despite a greater reduction in MAP and PVR. Moreover, the finding, however, was that there was a significant and linear
responses to NTG and placebo were not affected by LNMMA. correlation between the effect of albuterol on AIx and of ACh
This indicates that NO mediates a significant part of the response on forearm blood flow (Figure 2). This suggests that differ-
to inhaled albuterol. Furthermore, the degree of inhibition ences in the response to albuterol are likely to be caused by
produced by LNMMA, 50%, is consistent with data from the differences in endothelial function and that PWA provides a
forearm vascular bed31 and systemic studies on the volume reasonable means of assessing endothelial function noninva-
waveform.11 However, in the present study, we included a sively. Although the correlation between the 2 methods in the
suitable placebo aerosol and control vasoconstrictor to investi- present study was not absolute, the strength of the relation-
gate the potential confounding effect of baseline changes in heart ship is greater than that reported previously when endothelial
rate, MAP, and AIx after LNMMA. function was compared in different vascular beds.5 Thus,
Hypercholesterolemia is the condition most consistently associ- PWA may be suitable for use in large studies investigating
ated with endothelial dysfunction.2,3,32 Therefore, we investigated the predictive value of endothelial function.
Based on our previous data,20,25 it is unlikely that the small
the response to albuterol and NTG in a group of 27 hypercholes-
alterations in MAP and heart rate observed in the present
terolemics and matched controls and, in a separate cohort, compared
study could account for the effect of the 2 drugs on AIx.
endothelial function as assessed by PWA with that measured by
Moreover, in study 2 the changes in MAP and heart rate with
intra-arterial infusion of ACh and SNP in the forearm. Baseline AIx
albuterol were greater during infusion of NE, which would
was significantly higher in the hypercholesterolemic subjects, indi-
tend to reduce the observed difference between LNMMA and
cating increased arterial stiffness. This is the first time that increased
NE. Furthermore, in study 3 the changes in MAP and heart
aortic AIx has been reported in hypercholesterolemics, but in-
rate were similar between the 2 groups. Therefore, it seems
creased stiffness has been previously demonstrated by several other
likely that NTG and albuterol altered the waveform, in part by
techniques,33,34 although this is not a universal finding.35 However,
a direct effect of NO on large-artery mechanics.
the higher AIx may have been due to the slightly higher MAP20 in In summary, albuterol and NTG produce repeatable changes
the hypercholesterolemics, arterial stiffening per se, or a combina- in the arterial waveform. The response to albuterol but not to
tion of both.34,36 AIx fell less after albuterol in the hypercholester- NTG can be substantially inhibited by LNMMA, indicating that
olemics than in controls, despite their being well matched. More- albuterol reduces AIx in part through generation of NO. There-
over, mean plasma albuterol concentration was similar in both fore, albuterol can be considered an endothelium-dependent,
groups, as were the effects of albuterol and NTG on other hemo- NO-mediated vasodilator and NTG, endothelium independent.
dynamic variables, suggesting blunting of a direct effect of albuterol Moreover, hypercholesterolemics exhibit a reduced response to
on AIx in the hypercholesterolemic subjects, rather than, for albuterol but not to NTG, consistent with the presence of
example, an indirect mechanism through changes in heart rate or endothelial dysfunction. Finally, the response to albuterol was
MAP. Moreover, in the multiple regression model, which included correlated with the reponse to ACh in the forearm, suggesting
known and potential confounding variables, LDL cholesterol was that there is good agreement between the 2 methods of assessing
inversely and independently correlated with the change in AIx. endothelial function. These data support the view that PWA
Interestingly, although endothelial function declines with age, we coupled with administration of albuterol and NTG provides a
were unable to show any relationship between age and the albuterol simple, noninvasive, repeatable method for assessing endothelial
response in our multiple regression model. However, this is likely function. We believe that this technique provides a suitable
due to the relatively narrow age range of the study subjects and the means for assessing endothelial function in large numbers of
small sample size. patients and thus, answers the important question of the predic-
The inverse association between the response to albuterol tive value of endothelial function. PWA has already been
and plasma glucose is of considerable interest. Endothelial included in substudies of the ASCOT, SEARCH, and FIELD
dysfunction is associated with type 137 and type 2 diabetes38 investigations. This will address the importance of stiffness as a
6. 152 Arterioscler Thromb Vasc Biol. January 2002
predictor of risk, but we now need to include the noninvasive 20. Wilkinson IB, MacCallum H, Hupperetz PC, Van Thoor CJ, Cockcroft
assessment of endothelial function by PWA in such studies. JR, Webb DJ. Changes in the derived central pressure waveform and
pulse pressure in response to angiotensin II and noradrenaline in man.
J Physiol. 2001;530:541–550.
Acknowledgments 21. Chin-Dusting JP, Cameron JD, Dart AM, Jennings GL. Human forearm
This study was partly funded by the British Heart Foundation, the venous occlusion plethysmography: methodology, presentation and anal-
High Blood Pressure Foundation and a local research and develop- ysis. Clin Sci. 1999;96:439 – 440.
ment grant (Lothian Universities NHS Hospital Trust). Professor 22. Bland JM, Altman DG. Statistical methods for assessing agreement
between two methods of clinical measurement. Lancet. 1986;1:307–310.
D.J. Webb is currently in receipt of a Research Leave Fellowship
23. Cockcroft JR. Third European Meeting on Pulse Wave Analysis and
from the Wellcome Trust (052633). We would like to thank Sian Large-Artery Function: clinical applications of pulse wave analysis. J
Tyrrell, Simon Johnston, Philip Storey, and Jenny Smith for assis- Hum Hypertens. 2001;15:818. Abstract.
tance with data collection and Dr S. Pleasance for his kind assistance 24. Hayward CS, Webb CM, Collins P. Assessment of endothelial function
with the albuterol assays. using peripheral pressure waveform analysis. Circulation. 2000;
102(suppl II):II-172. Abstract 830.
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