This document discusses various strategies for cardioprotection and reducing myocardial injury during ischemia and reperfusion. It introduces ischemic preconditioning, postconditioning, and remote ischemic conditioning as methods to reduce infarct size. Ischemic preconditioning involves brief episodes of ischemia and reperfusion to protect the heart. Postconditioning involves intermittent reperfusion during primary PCI. Remote ischemic conditioning uses brief limb ischemia to protect the heart from afar. The document discusses the signaling pathways and clinical evidence for these conditioning strategies. It also reviews pharmacological approaches like antioxidants, sodium-hydrogen exchange inhibitors, and adenosine to limit reperfusion injury.
Percutaneus coronary intervention in Non ST elevation myocardial infarctionRamachandra Barik
Unstable angina (UA), acute non-ST elevation myocardial infarction (NSTEMI), and acute ST elevation myocardial infarction (STEMI) are the three presentations of acute coronary syndromes (ACS). The first step in the management of patients with ACS is prompt recognition, since the beneficial effects of therapy are greatest when performed soon after hospital presentation. For patients presenting to the emergency department with chest pain suspicious for an ACS, the diagnosis of myocardial infarction can be confirmed by the electrocardiogram (ECG) and serum cardiac biomarker elevation; the history is relied upon heavily to make the diagnosis of unstable angina
Fabry Disease (FD), also known as Anderson-Fabry disease, is an inherited X-linked disorder characterized by the absence (in men) or defi ciency (in women) in α-galactosidase A, activity that causes a progressive accumulation of glycosphingolipids within lysosomes of cells in all the major organ systems and progressive organ damage that fi rst manifests in childhood or early adulthood. End Stage Renal Disease (ESRD) is a major cause of morbidity and premature mortality in FD. We present a male patient with FD who was transplanted with kidney from a living donor and had a sudden cardiac arrest on the 4th day after operation. We suggest detailed preoperative examination including coronary angiography, echocardiography for these patients and also a multidisciplinary care is required for perioperative management of FD patients.
Percutaneus coronary intervention in Non ST elevation myocardial infarctionRamachandra Barik
Unstable angina (UA), acute non-ST elevation myocardial infarction (NSTEMI), and acute ST elevation myocardial infarction (STEMI) are the three presentations of acute coronary syndromes (ACS). The first step in the management of patients with ACS is prompt recognition, since the beneficial effects of therapy are greatest when performed soon after hospital presentation. For patients presenting to the emergency department with chest pain suspicious for an ACS, the diagnosis of myocardial infarction can be confirmed by the electrocardiogram (ECG) and serum cardiac biomarker elevation; the history is relied upon heavily to make the diagnosis of unstable angina
Fabry Disease (FD), also known as Anderson-Fabry disease, is an inherited X-linked disorder characterized by the absence (in men) or defi ciency (in women) in α-galactosidase A, activity that causes a progressive accumulation of glycosphingolipids within lysosomes of cells in all the major organ systems and progressive organ damage that fi rst manifests in childhood or early adulthood. End Stage Renal Disease (ESRD) is a major cause of morbidity and premature mortality in FD. We present a male patient with FD who was transplanted with kidney from a living donor and had a sudden cardiac arrest on the 4th day after operation. We suggest detailed preoperative examination including coronary angiography, echocardiography for these patients and also a multidisciplinary care is required for perioperative management of FD patients.
Myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle. Find a good presentation on Acute myocardial infarction here.
EMGuideWire's Radiology Reading Room: Stress-Induced CardiomyopathySean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Stress-Induced Cardiomyopathy and is brought to you by Jenna Pallansch, MD, Claire Lawson, NP, Shelby Hixson, PA, Emily Lipsitz, PA, Ashley Moore-Gibbs, DNP, Laszlo Littmann, MD, and John Symanski, MD.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
2. Introduction
Coronary heart disease
• Leading cause of death worldwide
• 3.8 million men / 3.4 million women die of this disease /yr
Modalities of treatment Include
• Fibrinolysis
• PCI / CABG
• Medical treatment viz Antiplatelets ,ACEi /ARB etc.
• 90% of the patients experience fall in ejection fraction
post operatively
3. Introduction
Cardio protection : broad term that refers to all strategies
aimed at attenuation of injurious results of myocardial
ischemia and reperfusion
Injury consists of
• Arrhythmias : reversible / irreversible
• Impairment of cardiac contractile function / coronary blood
flow : reversible / irreversible
• Myocardial infarction – irreversible
4. Infarct size
Established with TTC assay :
Gold standard in experimental settings
Triphenylterazolium ( TPH ) Triphenyl fomazan (TPF)
Succinate
Dehydrog
enase
5. Determinants of Infarct size
Area of myocardial ischemia :
the size of perfusion territory of the
coronary artery distal to the site of occlusion
Duration of ischemia to which area at risk
Amount of residual blood flow to the area at risk i.e the
collateral blood supply
Systemic hemodynamics notably the heart rate : minor
determinant
6. Reperfusion and reperfusion injury
Reduction in infarct size first reported by John Ross Jr and
his collaborates in 1972 by reperfusion
Reperfusion Injury :
First postulated in 1960 by Jennings et al as
• Cell swelling
• Contraction of myofibrils
• Disruption of sarcolemma
• Appearance of intramitochondrial calcium phosphate
particles
8. Clinical consequences of R.Injury
Myocardial stunning
No Reflow phenomenon
Reperfusion arrhythmias
Lethal reperfusion injury
9. Reperfusion injury
Myocardial stunning
• Best established manifestation
• Mechanical dysfunction that persists after reperfusion
despite absence of irreversible damage and despite
restoration of the normal or near normal coronary flow
• Lasts for several days to weeks
10. Reperfusion Injury
No reflow
Inability to reperfuse a previously ischemic region
Manifestation of severe micro vascular dysfunction
Results from marked endothelial dysfunction resulting in
• vasoconstriction
• Platelet and PMN activation
• Free radical production
11. Reperfusion Injury
Reperfusion Arrythmias
• VPC
• Susutained or non sustained VT
• AIVR
• Atrial fibrillation
• Ventricular fibrillation
AIVR may be a manifestaion of early reperfusion or
continuing arterial patency
12. Reperfusion Injury
Lethal reperfusion injury
A form of myocardial death and necrosis with reperfusion of
severely injured myocardium
Contraction band necrosis : a severe disruptive necrosis
due to calcium reentry
13. Gentle reperfusion by slow restoration of coronary blood
flow or perfusion pressure in the first 20-30 min of
reperfusion after myocardial ischemia reduces infarct size
Heusch G J Am Coll Cardiol 2004
15. Ischemic preconditioning
The heart’s own self-preserving mechanism
Cardioprotection by brief episode of ischemia and
reperfusion
Most consistent and the magnitude of protection is great
Reduce infarct size in most models
Reduce ventricular arrhythmias
Discovered as a case of serendipity
18. Time frames of ischemic preconditioning
Early or the “classical pre-conditioning” :Involves
• activation of existing signaling molecules
• wanes 1-2 hours after the ischemic insult
Late : the “second window” of protection (SWOP)related to
• Expression of signalling molecules
• Changes in gene expression
• Increased synthesis of cardioprotective stress proteins.
• begins 12-24 hours later and lasts for up to 72 hours
• More sustained but less powerful protection from infarction
19.
20. A third window of protection observed 6hrs after coronary
microembolistaion
Skyschalluy A et al Circ Res 2007
Tolerance to pre-conditioning may occur where prolonged
hours of ischaemia can result in a loss of preconditioning
effect.
IPC can also be induced by other forms of stress like
• Hypoxia, stretch, heat shock and a1 receptor stimulation
Time frames of ischemic preconditioning
21. Clinical Evidence For Preconditioning
• Less chest pain, ST-segment elevation, lactate production with
subsequent compared to first angioplasty balloon inflation
• Reduction in infarct size, mortality and CHF in patients with
history of angina before acute MI
• Acute tolerance to angina (warm up phenomenon)
• Studies performed on human cardiac tissue:
• ATP levels during CABG
• In vitro studies on isolated human muscle
• In vitro studies on human myocytes
22. History of Any Angina - TIMI 4
No Angina Angina
TotalCKunits
0
100
120
140
160
Kloner, et al.
154
119
Kloner RA, Shook T, Przyklenk K, Davis VG, Junio L, Matthews RV, Burstein S,
Gibson M, Poole WK, Cannon CP, McCabe C, Braunwald E, for the TIMI 4
Investigators. Previous angina alters in-hospital outcome in TIMI 4. A clinical
correlate to preconditioning? Circulation 1995; 91:37-45.
23. History of Any Angina - TIMI 4
(%)
0
2
4
6
8
10
12
14
No Angina
Angina
8%
3%
7%
1%
12%
4%p = 0.03
p = 0.006
p = 0.004
In-Hospital
Death
Severe CHF/
Shock
Death
Severe CHF
Shock
Kloner RA, Shook T, Przyklenk K, Davis VG, Junio L, Matthews RV, Burstein S,
Gibson M, Poole WK, Cannon CP, McCabe C, Braunwald E, for the TIMI 4
Investigators. Previous angina alters in-hospital outcome in TIMI 4. A clinical
correlate to preconditioning? Circulation 1995; 91:37-45.
25. Signal transduction in Cardioprotection
Three hierarchical levels
• Triggers
• Intracellular mediator cascade
• Effectors
Triggers : molecules released from various cell types
during ischemia and act on sarcolemmal membrane
receptors
This initiates an Intracellular cascade mostly protein
kinases that ultimately act on effectors – subcellular
elements viz mitochondria / cytoskeleton that stabilise the
jeopardized cardiomyocyte and prevent its death.
26.
27.
28. Signal transduction in Cardioprotection
Three parallel signaling pathways
• G protein coupled / natriuretic peptide receptors : centred on
Nitric oxide , NO synthase , cGMP, protein kinase G
• Reperfusion injury salvege kinase pathway : g protein coupled
/ growth factor receptors
• Survival activating factor enhancement pathway : TNF alpha /
JAK –STAT pathway
29. Limitations of ischemic preconditioning
NO reliable way to predict Myocardial infarction hence No
way to induce IPC or apply a stimulus
Aortic cross clamping / coronary artery cross clamping are
• Invasive
• Risk of coronary microembolization
• Risk of inducing infarction
• Risk of aortic embolization
30. Postconditioning
Postconditioning is the phenomenon whereby
several brief coronary artery
reperfusion/reocclusion cycles at the end of a
long coronary artery occlusion (stuttering
reperfusion) reduces infarct size
Zhao, Z-Q et al. Am J Physiol 2003;285:1574
Yang, X-M et al. JACC 2004;44:1103
32. Postconditioning
Primary PCI for STEMI
Repeat 30-60 sec balloon inflation at low pressure results
in:
• Greater attenuation of ST-segment elevation
• Improved distal coronary artery flow
• A significant reduction of 36% in infarct size
• 7% improvement in EF at one year
39. End points of post conditioning
Decreased Infarct size
Decreased tissue edema
Decreased PMN accumulation
Improved endothelial function
Decreased endothelial response to Ach
Decreased free radical production
44. Remote ischemic preconditioning
Both IPC and post conditioning involve manipulation of the
culprit coronary artery : a risk of acute myocardial infarction
45.
46.
47.
48.
49. Experimental protocol
Staat P, Rioufol G, Piot C, Cottin Y, Cung TT, L'Huillier I, Aupetit JF, Bonnefoy
E, Finet G, André-Fouët X, Ovize M. Postconditioning the human heart.
Circulation. 2005 Oct 4;112(14):2143-8.
50. Staat P, Rioufol G, Piot C, Cottin Y, Cung TT, L'Huillier I, Aupetit JF, Bonnefoy
E, Finet G, André-Fouët X, Ovize M. Postconditioning the human heart.
Circulation. 2005 Oct 4;112(14):2143-8.
Serum CK release over the first 72 hours of reperfusion
52. Kloner RA, Dow J, Bhandari A. Postconditioning markedly attenuates ventricular arrhythmias after
ischemia-reperfusion. J Cardiovasc Pharmacol Ther. 2006 Mar;11(1):55-63.
53. Concordant improvements in coronary flow reserve and ST-segment
resolution during percutaneous coronary intervention for acute
myocardial infarction:
a benefit of postconditioning
• 24 patients with evolving anterior STEMI were randomized to
ischemic postconditioning or usual care during PCI
• Postconditioned pts had a greater and more rapid resolution of ST
segment elevation (70% vs. 48%, p = 0.0002) by the end of the
procedure
• Postconditioned pts had greater hyperemic coronary vasodilator
reserve (2.2 vs. 1.5, p< 0.001)
• Peak serum creatine kinase was lower in postconditioned pts (1,524
vs. 1,862 IU/L in controls, p = 0.03)
• Conclusion: Postconditioning performed during PCI for STEMI
improved ST-segment resolution and coronary flow reserve,
measures of microcirculatory function, as well as reducing tissue
necrosis.
Laskey WK, Yoon S, Calzada N, Ricciardi MJ. Concordant improvements in coronary flow reserve and ST-
segment resolution during percutaneous coronary intervention for acute myocardial infarction: a benefit of
postconditioning. Catheter Cardiovasc Interv. 2008 Aug 1;72(2):212-20
54. Remote ischaemic conditioning before hospital admission, as a
complement to angioplasty, and effect on myocardial salvage in
patients with acute myocardial infarction: a randomised trial
• 333 patients with first AMI randomized to primary PCI with or
without remote conditioning (4 cycles of 5-minute brachial artery
cuff inflation & 5 minutes deflation)
• Median salvage index by myocardial perfusion imaging 0.75 in
remote conditioning group versus 0.55 in control group, p = 0.03
• Conclusion: Remote ischemic conditioning before hospital
admission increases myocardial salvage and is safe.
Bøtker HE, Kharbanda R, Schmidt MR, Bøttcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen
NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L,
Nielsen SS, Rehling M, Sørensen HT, Redington AN, Nielsen TT. Remote ischaemic conditioning
before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in
patients with acute myocardial infarction: a randomised trial. Lancet. 2010 Feb 27;375(9716):727.
55. Bøtker HE, Kharbanda R, Schmidt MR, Bøttcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen
NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L,
Nielsen SS, Rehling M, Sørensen HT, Redington AN, Nielsen TT. Remote ischaemic conditioning
before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in
patients with acute myocardial infarction: a randomised trial. Lancet. 2010 Feb 27;375(9716):727.
56. RIPerC in PPCI patients
Botker et al Lancet 2010
• 246 STEMI patients
randomised in ambulance
to RIPC 4x5 min cuff on
arm or control.
- Myocardial salvage index improved at 30 days (0.56 to 0.76).
- Reduced myocardial infarct size at 30 days (SPECT P=0.05)
- No effect on Troponin-T, TIMI flow, LVEF, MACE at 30 days.
- All coronary territories, TIMI 2-3 flow and collaterals included.
-LAD infarcts greater reduction in infarct size.
57. Pharmacological strategies of
Myocardial salvage
Inotropic stimulation of the reperfused stunned heart
Antioxidants : major antioxidant being Glutathione
peroxidase and not superoxide dismutase
Vitamin E is required in prolonged and verly high oral
dosage to achieve therpeutic salvage concentration
Sodium hydrogen antiport inhibition :
Cariporide a Na H exchange inhibitor at 120 mg dose for 6 -8
days periopertively reduced the rate of death and MI
undergoing CABG
GUARDIAN trial J Cardiac Surg 2003
58. Pharmacological strategies of
Myocardial salvage
Simulating endogenous cardioprotectants
• Adenosine via opening of mitochondrial K ATP channels
through interaction with A1 and A3 receptors
• Nitric oxide may serve to diminish reperfusion injury
through improved endothelial function , decreased platelet
and neutrophil activation , augmenting coronary flow
Vinten Johansen J Ann Thorac Surg 1999
59. Therapeutic applications of
preconditioning
Diabetes mellitus and preconditioning
• IPC is mediated at least in part by activation of the
KATP channel and this channel may be altered in the
diabetic heart;
• Certain oral hypoglycemic drugs (such as glibenclamide)
prevent IPC by blocking the KATP channel and has been
associated with an increase in early mortality in diabetics
following primary PCI for AMI
60. Therapeutic applications of
preconditioning
Role of nitroglycerin.
Four-hour infusion of nitroglycerin 24 to 48
hours before exercise stress testing with stable angina
showed an increase in workload during the test and
significant improvements in the (ECG) manifestations of
ischemia.
61. Pharmacological strategies of
Myocardial salvage
• Therapeutic hypothermia
• Magnesium therapy
• Pharmacological treatment of no reflow
1. Calcium antagonist : verapamil / diltiazem
reverse condition in 67% of cases
given as intracoronary infusion
2. Nicorandil given as intracoronary 2mg iv bolus
3. Sodium nitroprusside
4. GpIIb/IIIa inhibitors
62. Endovascular cooling
Endovascular coils and external cooling blankets are
used to bring the core temperature of a patient down to 33
degrees during PCI for acute myocardial infarction showed
reduction in infarct size in the subgroup of patients with an
anterior MI.
73. End points of cardioprotection
Periprocedural myocardial injury during PCI / CABG as
estimated by trop I / Lv systolic dysfunction affect long term
survival
Estimation of infarct size by
• Thallium scan
• SPECT
• MRI
74. CONCLUSIONS
Ischemic Conditioning
• Reducing myocardial infarct size
• Reducing cardiac damage during PCI
• Protecting the myocardium during CABG and other
procedures requiring cardiopulmonary bypass
• Protecting the vasculature during vascular surgery
procedures
75. Ischemic Postconditioning in Surgery
Luo et al J Thorac Cardiovasc Surg 2007:133;1373.
• 24 children TOF surgery:
Control- Normal surgery
IPost- 2x30 sec aortic re-
clamping.
• Reduced trop-I by 50% and
CK-MB by 34%.
• Invasive treatment protocol.
• Other studies reporting
benefit in adult valve surgery.
76. 1. Improved myocardial perfusion and ST resolution 1,2
2. Reduced myocardial infarct size:
40% less CK-MB, 47% less trop I 4.
31% to 23% at 1 week (SPECT) 3.
20% to 12% at 6 mths (SPECT) 4.
63% to 51% (IS/AAR) at 3 months (N=86) 5.
3. Preserved LV ejection function by 7% (echo) at 1 year 4.
1. Staat et al Circ 2005
2. Ma et al J Interven Cardiol 2006
3. Yang et al J Interven Cardiol 2007
4. Thibault et al Circ 2008
5. Lonborg et al Circ Card Int 2010
Ischaemic Postconditioning in PPCI