Bradykinin Preconditioning Preserves Coronary Microvascular Reactivity During Cardioplegia–Reperfusion

Background Alterations of microvascular reactivity reduce myocardial perfusion after ischemic cardioplegia. We hypothesized that bradykinin preconditioning (BKPC) would preserve endothelium-dependent microvascular responses and improve myocardial function after cardioplegic ischemia–reperfusion. Methods Rabbit hearts were perfused with Krebs-Henseleit buffer (KHB). The hearts were arrested for 60 minutes with moderately cold (25°C) crystalloid cardioplegia (MCCP, n = 8) or with cold (0° to 4°C) crystalloid cardioplegia (CCCP) (n = 6). The BKPC hearts received a 10-minute coronary infusion of 10−8 M BK-enriched KHB, followed by a 5-minute recovery period, and then were arrested for 60 minutes with MCCP (BKPC + MCCP, n = 8) or with CCCP (BKPC + CCCP, n = 6). The hearts were reperfused for 30 minutes with KHB. Six control hearts were perfused with KHB for 90 minutes without cardioplegia-ischemia. Left ventricle performance was measured, and in vitro relaxation responses of precontracted coronary arterioles (internal diameter, 80 to 150 μm) were obtained in a pressurized no-flow state. Results Ischemic arrest with MCCP or CCCP markedly reduced endothelium-dependent relaxation to adenosine 5′-diphosphate, substance P, and calcium ionophore (A23187). Both MCCP and CCCP significantly enhanced contractile responses to U46619 (10−7 M), a thromboxane A2 analogue, compared with control (p< 0.05). In contrast, BKPC significantly improved the recovery of endothelium-dependent relaxation to adenosine 5′-diphosphate, substance P, and A23187 compared with MCCP or CCCP, respectively. BKPC reduced the contractile responses to U46619 compared with MCCP or CCCP. BKPC also improved postischemic performance compared with MCCP or CCCP alone (p< 0.05). Conclusions BKPC preserves endothelium-dependent microvascular responses and prevents the hypercontractility to U46619. These effects may provide increased coronary perfusion and prevent arteriolar spasm after open heart surgery. They suggest that BK preconditions the coronary microvasculature during cardiovascular surgery.