EFFECTS OF ISCHEMIC PRECONDITIONING ON MYOCARDIAL PERFUSION, FUNCTION, AND MICROVASCULAR REGULATION

Background-Ischemic preconditioning (PC) has been advocated as a metho d to preserve myocardial function and perfusion during minimally invas ive direct coronary bypass (MIDCAB), We examined the effects of PC on indexes of myocardial function, perfusion, and endothelial and beta-ad renergic coronary regulation after 30 minutes of ischemia and 60 minut es of reperfusion (IR), Methods and Results-Five groups of pigs were s tudied: (1) PC-IR: PC by 3 cycles of 5-minute left anterior descending coronary artery occlusion (CO) and 5-minute reperfusion (Rep)+30 minu tes of CO+60 minutes of Rep; (2) IR alone: 30 minutes of CO+60 minutes of Rep; (3) PC alone; (4) PC-IR-glibenclamide (GLIB): PC-IR+infusion of GLIB; (5) control: noninstrumented. Reactivity (in vitro) of corona ry arterioles (70 to 150 mu m) from the myocardial area at risk was ex amined with video microscopy. beta-Adrenergic microvascular relaxation s to isoproterenol, forskolin, and 8-bromo-cAMP were significantly red uced after IR alone (P<0.05 versus control, 2-way ANOVA). PC before IR restored these responses to normal (P<0.05 PC-IR versus IR alone), an d GLIB abolished this effect of PC. Subepicardial endothelium- depende nt microvascular relaxation to ADP was significantly reduced after IR alone (P<0.01 versus control) but was preserved in both the PC-IR and PC-IR-GLIB groups (P<0.05 versus IR alone). The response of vessels to ADP from the subendocardium was significantly reduced in all groups c ompared with the control response (all P<0.05 versus control). Nitropr usside elicited a similar response in vessels from all groups. PC befo re IR did not affect the reduced myocardial percent segmental shorteni ng or left ventricular maximal dP/dt, did not affect myocardial perfus ion in the subepicardium or subendocardium, and did not change express ion of the inducible or the constitutively expressed isoforms of nitri c oxide synthase. Conclusions-PC before IR preserves beta-adrenergic s ignal transduction in coronary smooth muscle through a K-ATP channel m echanism, whereas PC preserves endothelium-dependent relaxation in the subepicardium through a mechanism not related to K-ATP channels or th e enhanced expression of nitric oxide synthase. Nevertheless, PC does not improve shea-term myocardial function or baseline myocardial perfu sion after IR. Thus, the short-term beneficial role of PC in myocardia l protection during MIDCAB may be limited.