S Reducion of infarction size as a target Mohamed Mahmoud Abd El Ghany Mohamed Mahmoud Abd El Ghany...
Transcript of S Reducion of infarction size as a target Mohamed Mahmoud Abd El Ghany Mohamed Mahmoud Abd El Ghany...
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Reducion of infarction size as Reducion of infarction size as a targeta target
Mohamed Mahmoud Abd El GhanyMohamed Mahmoud Abd El Ghany Cardiology Cardiology Professor ofProfessor of
Cairo UniversityCairo University
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The size of the infarction is a major determinant of both the risk of death and the likelihood of subsequent heart failure
ss initial perfusion defect - final infarct size
Salvage index = initial perfusion defect
J Nucl Med 2004; 45:725–729
Conclusion: This study clearly demonstrated that salvage index predicts mortality in patients with acute myocardial infarction after reperfusion therapy
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Research during the past two decades has tried to elucidate the critical steps in the injury and subsequent killing of myocardial cells, with
the hope that antagonizing these steps may provide new cardioprotective therapies
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Ischemic preconditioning
Preischemic Selenium Status
Myocardial reperfusion
- Time to reperfusion - Method of reperfusion
- BP
Myocardial O2 consumption
Connexin 43
C reactive protein
Determinants of Myocardial Infarct Size
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Ischemic preconditioningIschemic preconditioning
Enhancement of myocardial tolerance against infarctioninduced by a brief sublethal episodes of ischemia
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First window of preconditioning Second window of preconditioning
Reduction of infarct size and post-ischemicReduction of infarct size and post-ischemic inflammation from a highly selectiveinflammation from a highly selective
adenosine A2A receptor agonist, ATL-146e, adenosine A2A receptor agonist, ATL-146e, in reperfused canine myocardiumin reperfused canine myocardium
Am J Physiol Heart Circ Physiol (December 9, 2004)
In canine models of myocardial infarction, low dose, intravenous administration ofthe highly selective adenosine A2A receptor agonist, ATL-146e, significantly reducedinfarct size , both as a pretreatment and when administered just prior to reperfusion,
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Ischemic preconditioning
Preischemic Selenium Status
Myocardial reperfusion
- Time to reperfusion - Method of reperfusion
- BP
Myocardial O2 consumption
Connexin 43
C reactive protein
Determinants of Myocardial Infarct Size
ssAntioxidants & Redox Signaling 2004, 6(4): 792-796
High selenium Diet
Low seleniumDiet
10 W
Coronaryocclusion
Coronaryocclusion
Infarct size 25.16 ±1.19 %
Infarct size 36.51 ±4.14 %
Conclusion: Preischemic body selenium status is a major determinant of the outcome of myocardial ischemia in vivo in rats probably because it influences the cellular antioxidant activity.
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Ischemic preconditioning
Preischemic Selenium Status
Myocardial reperfusion
- Time to reperfusion - Method of reperfusion
- BP
Myocardial O2 consumption
Connexin 43
C reactive protein
Determinants of Myocardial Infarct Size
ssHeart 2000;84:142–148
Conclusion:In this single large trial, the beneficial effect of time to thrombolysis on infarct size and ejection fraction was restricted to treatment given within two hours of symptom onset,
ssJ Nucl Med 2004; 45:725–729
Conclusion:Mechanical reperfusion is associated with higher value of myocardial salvage compared to thrombolytic
Eur Heart J, 2002: 23: 1112–1117
Distal embolizationP value
No (n=167)Yes (n=27)
Patency151) 92%(19) 73%(0.009
LVEF(%) 51±942±140.005
Mortality)5 years(
15) 9%(12) 44%(<0.001
Death or recurrent MI
)5 years(24) 14%(14) 52%(<0.001
ssJ Am Coll Cardiol 2009 :53 ;309-15
Slow flow/no reflow(%)
v
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Slow flow/no reflow(%)
J Am Coll Cardiol 2009 :53 ;309-15
MVO
IS
Conclusion: Manual aspiration thrombectomy preserves microvascular Integrity and reduces final IS after STEMI; thus, it may represent a useful adjunct to pharmacotherapy
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Inadvertent drop in systemic BP Elevated systemic BP and resultant LVH
Equally detrimental on the infarct size and exerts a deleterious effect on the progression of myocardial necrosis
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Ischemic preconditioning
Preischemic Selenium Status
Myocardial reperfusion
- Time to reperfusion - Method of reperfusion
- BP
Myocardial O2 consumption
Connexin 43
C reactive protein
Determinants of Myocardial Infarct Size
ssRadius Pressure ͯ
Wall stress = 2 ͯ Thickness
Beta blockersNitroglycerine
Esmolol and Cardiopulmonary Bypass DuringReperfusion Reduce Myocardial Infarct Size
in Dogs DeBakey Institute, Texas A&M University, College Station, Texas
B - Blockade may be cardioprotective duringreperfusion through various mechanisms and mayenhance myocardial salvage, even when treatment isinitiated as late as with the onset of reperfusion.
(Ann Thorac Surg 2001;72:1964 –9)
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Ischemic preconditioning
Preischemic Selenium Status
Myocardial reperfusion
- Time to reperfusion - Method of reperfusion
- BP
Myocardial O2 consumption
Connexin 43
C reactive protein
Determinants of Myocardial Infarct Size
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*p 0.037.
J Am Coll Cardiol 2003;41:681– 6
In humans, Reduced Cx43 expression ( Electrical uncoupling) induced by acute ischemia enhances
arrhythmogenesis, but it may also protect the heart by limiting intercellular spread of chemical mediators of
injury
Conclusion: Cx43-deficient mice develop smaller infarcts than wild-type mice following coronary ligation
New therapies designed to decrease the risk of arrhythmias by enhancing intercellular communication could lead to larger infarcts caused by persistent coronary occlusion
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Ischemic preconditioning
Preischemic Selenium Status
Myocardial reperfusion
- Time to reperfusion - Method of reperfusion
- BP
Myocardial O2 consumption
Connexin 43
C reactive protein
Determinants of Myocardial Infarct Size
ssRichard et al. NEJM 2006 :355;5
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CRP levels increase dramatically in patients with
myocardial infarction beginning 6 hours after the onset of ischemia and peaking at approximately 50 hours
CRP values after acute myocardial infarction predict outcome, including death and heart failure
Pepys et al. designed a small molecule, 1,6-bis(phosphocholine)-hexane ( Bis(PC)-H), that binds CRP and prevents interactions between CRP and its various ligands, as well as CRP-induced complement activation
(Suleiman M et al. J Am Coll Cardiol 2006;47:962-8)
(Pepys et al,Nature 2006;440:1217-21)
ssRichard et al. NEJM 2006 :355;5
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Reduction of infarct size is very important
The size of the infarction is a major determinant of both the risk of death and the likelihood of subsequent heart failure
Measures for infarct size reduction should start before occurance of event
Thank you