ss

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

ss

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

ss

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

ss

Ischemic preconditioningIschemic preconditioning

Enhancement of myocardial tolerance against infarctioninduced by a brief sublethal episodes of ischemia

ss

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,

ss

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.

ss

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

ss

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

ss

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

ss

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)

ss

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

ss

*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

ss

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

ss

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

ss

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