Simulated Ischemia Does Not Protect Against Efferent Sympathetic Denervation Following Acute Myocardial Infarction in Canine Hearts

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Abstract
Preconditioning the myocardium with brief episodes of ischemia preserves efferent autonomic responsiveness of noninfarcted myocardium apical to a site of acute transmural ischemia by mechanism(s) still unknown. We hypothesized that repeated brief exposure of the myocardium to a simulated ischemic milieu including hypoxia, high K+, low pH, and adenosine would be as effective as brief coronary occlusions in creating this protection. Open chest anesthetized dogs received an extracorporeal bypass between the left carotid artery and a diagonal branch of the left anterior descending coronary artery. We analyzed the effects of simulated ischemia on the time course and extent of efferent sympathetic denervation during a subsequent 3-hour sustained ischemia in three groups of dogs: two groups of dogs underwent four cycles of 5-minute intracoronary perfusion with either hypoxic altered Tyrode's solution (12 mM K+, 6.8 pH, and 10 microM adenosine; n = 11) or normal Tyrode's solution (n = 11). Each Tyrode's perfusion was separated by 5 minutes of blood perfusion prior to permanent coronary occlusion by latex embolization of the cannulated coronary artery. A third group received a continuous 3-hour blood perfusion before the final ischemic episode (n = 5). Shortening of effective refractory periods (ERPs) induced by bilateral ansae subclaviae stimulation (2 to 4 Hz) basal and apical to the intervention site was determined before and after perfusions and 20, 60, 120, and 180 minutes after sustained occlusion. In all groups, sympathetically-induced ERP shortening was unchanged at basal sites throughout the experiment. ERP shortening at apical sites was unchanged after perfusions with either the altered or normal Tyrode's solution or after a continuous 3-hour blood perfusion. However, ERP shortening became significantly attenuated at apical sites after coronary occlusion in all groups. Neither the size in reduction of sympathetically-induced ERP shortening at apical test sites nor the cumulative percentage of denervated apical test sites (< or = 2-msec shortening) during a 3-hour period of permanent ischemia differed significantly among groups (P = 0.052 and P = 0.752, respectively). The degree of subepicardial involvement in the myocardial infarction was comparable among groups. Thus, brief exposure of the left ventricular myocardium to ischemic metabolites prior to a subsequent permanent coronary occlusion does not trigger mechanism(s) that are responsible for protection against efferent sympathetic denervation apical to an area of transmural myocardial infarction/ischemia.