Preconditioning does not attenuate myocardial stunning

Background. Despite numerous reports that one or more episodes of brief coronary artery occlusion preconditions the myocardium and dramatically reduces myocardial infarct size produced by a subsequent prolonged ischemia, we recently demonstrated that preconditioning does not attenuate contractile dysfunction in the peri-infarct tissue. However, the specific effects of preconditioning on myocardium in which wall motion has not been compromised by the preconditioning regimen per se and is further submitted to a short ischemic insult (that is, not confounded by necrosis) remain unknown. Methods and Results. We addressed these issues in the canine model of myocardial stunning. Eighteen anesthetized dogs underwent 15 minutes of coronary occlusion followed by 3 hours of reperfusion. Before the 15-minute coronary occlusion, each dog received one of three treatments: no intervention (control group, n=6), one episode of 5-minute coronary occlusion/5-minute reperfusion (PC₅ group, n=6), or one episode of 2.5-minute coronary occlusion/5-minute reperfusion (PC_2.5 group, n=6). Segment shortening (SS) in the ischemic/reperfused midmyocardium was monitored by sonomicrometry, and myocardial blood flow was assessed by injection of radiolabeled microspheres. All three groups were equally ischemic during the 15-minute coronary occlusion: Midmyocardial blood flow averaged 0.05±0.02, 0.07±0.04, and 0.08±0.03 ml/min/g in control, PC_2.5, and PC₅ groups, respectively. Before the 15-minute coronary occlusion, PC₅ dogs exhibited significant stunning (SS=55% baseline; p<0.01 versus control), whereas PC_2.5 dogs did not (SS=91% baseline; p=NS versus control). However, segment shortening during the subsequent 15-minute coronary occlusion was equally depressed at -25% to -42% of baseline values among the three groups. Furthermore, all three groups demonstrated a similar degree of stunning after reperfusion: SS at 3 hours after reflow averaged 24±12%, 34±16%, and 48±12% of baseline in control, PC_2.5, and PC₅ groups, respectively (p=NS). The degree of recovery of function after reperfusion correlated with the amount of midmyocardial blood flow during coronary artery occlusion. However, this relation was not different among the three groups: Specifically, for any given collateral flow during ischemia, preconditioning did not reduce the degree of stunning. Conclusions. Preconditioning neither preserves contractile function during a reversible ischemic insult nor prevents myocardial stunning during the initial hours of reflow.