Postconditioning by Volatile Anesthetics: Salvaging Ischemic Myocardium at Reperfusion by Activation of Prosurvival Signaling

Abstract

Z N u EPERFUSION AFTER PROLONGED coronary artery occlusion is a prerequisite for salvaging ischemic myocardium. nfortunately, reperfusion also paradoxically exacerbates the iniial damage caused by the ischemia itself.1-3 Experiments conucted in the 1980s by Buckberg and associates4-7 provided the rst evidence that modification of reperfusion conditions may educe the extent of injury resulting from restoration of coroary blood flow. Studies of controlled coronary hemodynamics fter myocardial ischemia indicated that gradual reperfusion at ow intracoronary pressures reduces the size of the resulting yocardial infarction.4 For example, selective low-pressure 40-50 mmHg) coronary artery reperfusion before total reversal f coronary occlusion not only reduced infarct size but also nhanced postischemic systolic function in the absence or resence of inotropic drugs and attenuated myocardial tissue dema compared with abrupt reperfusion.5 Similarly, eliminaion of reactive hyperemia during early reperfusion by mainteance of coronary blood flow at levels present before the onset f coronary occlusion preserved myocardial metabolism, reuced intracellular calcium (Ca2 ) accumulation, and improved egional wall motion compared with uncontrolled reperfusion.8 radual reperfusion of the ischemic territory during the first 30 inutes after prolonged coronary occlusion also reduced myoardial necrosis in vivo and preserved endothelial function in ostischemic coronary arterial rings in vitro.9 These and other tudies6,7,10,11 suggested that “gentle” or “staged” control of oronary hemodynamics during early reperfusion was a critical eterminant of myocardial integrity and contractile function fter a brief or prolonged ischemic episode.8 Despite the comelling nature of these observations, the vast majority of the xperimental and clinical research investigations examining the dverse consequences of ischemia-reperfusion injury and how hey may be mitigated have instead focused on interventions erformed before the onset of ischemia (ie, preconditioning). owever, coronary artery occlusion cannot be temporally preicted in most patients with acute myocardial infarction with ny degree of certainty, and, as a result, the application of schemic or pharmacologic preconditioning strategies has been imited to conditions in which the precise onset of ischemia is ell defined (eg, inflation of an angioplasty balloon during ardiac catheterization, application of the aortic cross-clamp uring cardiopulmonary bypass, and coronary occlusion to acilitate vascular anastomosis during off-pump coronary artery ypass graft surgery). t