s Reducion of infarction size as a target Mohamed Mahmoud Abd El Ghany Mohamed Mahmoud Abd El Ghany Cardiology Professor of Cairo University

s  The size of the infarction is a major determinant of both the risk of death and the likelihood of subsequent heart failure

s 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

s 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

s  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

s Ischemic preconditioning Enhancement of myocardial tolerance against infarction induced by a brief sublethal episodes of ischemia

s First window of preconditioning Second window of preconditioning

Reduction of infarct size and post-ischemic inflammation from a highly selective adenosine A2A receptor agonist, ATL-146e, in reperfused canine myocardium Am J Physiol Heart Circ Physiol (December 9, 2004) In canine models of myocardial infarction, low dose, intravenous administration of the highly selective adenosine A2A receptor agonist, ATL-146e, significantly reduced infarct size, both as a pretreatment and when administered just prior to reperfusion,

s  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

s Antioxidants & Redox Signaling 2004, 6(4): High selenium Diet Low selenium Diet 10 W Coronary occlusion Coronary occlusion Infarct size ±1.19 % Infarct size ±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.

s  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

s Heart 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,

s J 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± Mortality (5 years) 15 (9%)12 (44%)<0.001 Death or recurrent MI (5 years) 24 (14%)14 (52%)<0.001

s J Am Coll Cardiol 2009 :53 ; Slow flow/no reflow(%) v

s J Am Coll Cardiol 2009 :53 ; MVO IS Conclusion: Manual aspiration thrombectomy preserves microvascular Integrity and reduces final IS after STEMI; thus, it may represent a useful adjunct to pharmacotherapy

s 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

s  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

s MVO2 Inotropic Status Wall Stress Heart Rate Radius Pressure Wall stress = 2 Thickness Beta blockers Nitroglycerine

Esmolol and Cardiopulmonary Bypass During Reperfusion Reduce Myocardial Infarct Size in Dogs DeBakey Institute, Texas A&M University, College Station, Texas B - Blockade may be cardioprotective during reperfusion through various mechanisms and may enhance myocardial salvage, even when treatment is initiated as late as with the onset of reperfusion. (Ann Thorac Surg 2001;72:1964 –9)

s  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

s *p 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

s  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

s Richard et al. NEJM 2006 :355;5

s  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: )

s Richard et al. NEJM 2006 :355;5

s  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

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