Feng Jun, Bianchi Cesario, Li Jianyi, Sellke Frank W
Division of Cardiothoracic Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Ann Thorac Surg. 2005 Mar;79(3):911-6. doi: 10.1016/j.athoracsur.2004.09.017.
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.
Rabbit hearts were perfused with Krebs-Henseleit buffer (KHB). The hearts were arrested for 60 minutes with moderately cold (25 degrees C) crystalloid cardioplegia (MCCP, n = 8) or with cold (0 degrees to 4 degrees 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 mum) were obtained in a pressurized no-flow state.
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).
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.
微血管反应性改变会降低缺血性心脏停搏后的心肌灌注。我们推测缓激肽预处理（BKPC）可保留内皮依赖性微血管反应，并改善心脏停搏缺血再灌注后的心肌功能。
用Krebs-Henseleit缓冲液（KHB）灌注兔心脏。心脏用中度低温（25℃）晶体心脏停搏液（MCCP，n = 8）或低温（0℃至4℃）晶体心脏停搏液（CCCP）（n = 6）停搏60分钟。BKPC组心脏先接受10分钟10⁻⁸ M富含缓激肽的KHB冠状动脉灌注，随后有5分钟恢复期，然后用MCCP（BKPC + MCCP，n = 8）或CCCP（BKPC + CCCP，n = 6）停搏60分钟。心脏用KHB再灌注30分钟。6个对照心脏用KHB灌注90分钟，不进行心脏停搏-缺血处理。测量左心室功能，并在无血流加压状态下获得预收缩冠状动脉小动脉（内径80至150μm）的体外舒张反应。
用MCCP或CCCP进行缺血性停搏显著降低了对5'-二磷酸腺苷、P物质和钙离子载体（A23187）的内皮依赖性舒张。与对照组相比，MCCP和CCCP均显著增强了对血栓素A2类似物U46619（10⁻⁷ M）的收缩反应（p < 0.05）。相比之下，BKPC分别与MCCP或CCCP相比，显著改善了对5'-二磷酸腺苷、P物质和A23187的内皮依赖性舒张恢复。与MCCP或CCCP相比，BKPC降低了对U46619的收缩反应。与单独的MCCP或CCCP相比，BKPC还改善了缺血后功能（p < 0.05）。
BKPC保留内皮依赖性微血管反应，并防止对U46619的过度收缩。这些作用可能增加冠状动脉灌注，并防止心脏直视手术后小动脉痉挛。它们表明BK在心血管手术期间对冠状动脉微血管起预处理作用。
