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Reducion of infarction size as a target

Reducion of infarction size as a target. 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. Conclusion:

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Reducion of infarction size as a target

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  1. Reducion of infarction size as a target Mohamed MahmoudAbd El Ghany Cardiology Professor of Cairo University s

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

  3. Conclusion: • This study clearly demonstrated that salvage index predicts mortality in patients with acute myocardial infarction after reperfusion therapy s initial perfusion defect - final infarct size Salvage index = initial perfusion defect J Nucl Med 2004; 45:725–729

  4. 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

  5. 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

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

  7. s First window of preconditioning Second window of preconditioning

  8. Reduction of infarct size and post-ischemicinflammation from a highly selectiveadenosine 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,

  9. 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

  10. High selenium Diet Coronary occlusion Infarct size 25.16 ±1.19 % 10 W Low selenium Diet Coronary occlusion 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. s Antioxidants & Redox Signaling 2004, 6(4): 792-796

  11. 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

  12. 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 Heart 2000;84:142–148

  13. Conclusion: Mechanical reperfusion is associated with higher value of myocardial salvage compared to thrombolytic s J Nucl Med 2004; 45:725–729

  14. Eur Heart J, 2002: 23: 1112–1117

  15. Slow flow/no reflow(%) s v J Am Coll Cardiol 2009 :53 ;309-15

  16. Slow flow/no reflow(%) MVO • Conclusion: • Manual aspiration thrombectomy preserves microvascular Integrity • and reduces final IS after STEMI; thus, it may represent a useful • adjunct to pharmacotherapy s IS J Am Coll Cardiol 2009 :53 ;309-15

  17. Elevated systemic BP and resultant LVH Inadvertent drop in systemic BP Equally detrimental on the infarct sizeand exerts a deleterious effect on the progression of myocardial necrosis s

  18. 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

  19. s Beta blockers Nitroglycerine Radius Pressure ͯ Wall stress = 2 ͯ Thickness

  20. 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)

  21. 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

  22. 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 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 *p 0.037. s J Am Coll Cardiol 2003;41:681– 6

  23. 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

  24. s Richard et al. NEJM 2006 :355;5

  25. 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) s (Pepys et al,Nature 2006;440:1217-21)

  26. s Richard et al. NEJM 2006 :355;5

  27. Take home message • 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 s

  28. Thank you

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