Determinants of Delayed Preconditioning Against Myocardial Stunning in Chronically Instrumented Pigs

Abstract

To test the hypothesis that a critical stenosis prevents delayed preconditioning against stunning, studies were conducted in pigs chronically-instrumented with occluders and segment-shortening crystals. In the setting of a critical stenosis, a preconditioning stimulus of repetitive brief occlusions resulted in infarction. Thereafter, a single 10-minute occlusion was used as the preconditioning stimulus. Delayed preconditioning against stunning was documented on subsequent days by the deficit-of-function following brief repetitive occlusions. In contrast to experiments in the naïve heart, the deficit-of-function improved on the day after a single 10-minute occlusion (from 60±14 to 24±6 arbitrary units, p=0.003), and similar improvement occurred when reperfusion was performed through a critical stenosis (32±6 units, p=0.02 vs. naïve and p=0.34 vs. no stenosis). Delayed preconditioning also reduced the frequency of ventricular fibrillation, and produced a 4-fold increase in both calcium-dependent and calcium-independent NOS activity. Thus, a critical stenosis did not prevent delayed preconditioning against stunning.