Gutterman D D, Chilian W M, Eastham C L, Inou T, White C W, Marcus M L
Am J Physiol. 1986 Jan;250(1 Pt 2):H114-20. doi: 10.1152/ajpheart.1986.250.1.H114.
Thrombolytic therapy for acute coronary occlusion may be more effective if combined with substrate-enhanced reperfusion. In this study, we examined the utility of pyruvic acid, an important metabolic substrate, in salvaging ischemic myocardium. Twenty-six anesthetized dogs underwent 3 h of circumflex coronary occlusion followed by 90 min of reperfusion with administration of intracoronary pyruvate or vehicle. To test the sensitivity of the model in detecting differences in infarct size, eight additional dogs underwent coronary occlusion of shorter duration (45 min), an intervention that is known to reduce infarct size. Collateral perfusion to the ischemic zone during coronary occlusion was similar in experimental and control groups. Whereas a shorter duration of occlusion (45 min) decreased the infarct-to-risk area ratio by 54% compared with a longer duration of occlusion (90 min), neither early (15 min prior to occlusion) nor late (3 h after occlusion) onset of intracoronary infusion of pyruvate shifted the infarct-risk relationship (control: y = 74x - 8.7, r = 0.99; early infusion: y = 0.76x - 9.5, r = 0.85; late infusion: y = 0.58x - 5.5, r = 0.79). The failure of intracoronary administration of pyruvate to limit infarct size raises questions as to its potential clinical utility in the setting of acute myocardial ischemia.
急性冠状动脉闭塞的溶栓治疗若与底物增强再灌注相结合可能更有效。在本研究中，我们检测了重要代谢底物丙酮酸在挽救缺血心肌方面的效用。26只麻醉犬接受了3小时的左旋支冠状动脉闭塞，随后给予冠状动脉内丙酮酸或赋形剂再灌注90分钟。为测试该模型检测梗死面积差异的敏感性，另外8只犬接受了较短时间（45分钟）的冠状动脉闭塞，这一干预措施已知可减小梗死面积。冠状动脉闭塞期间缺血区的侧支灌注在实验组和对照组中相似。与较长闭塞时间（90分钟）相比，较短闭塞时间（45分钟）使梗死与危险区域的比例降低了54%，然而，无论是冠状动脉内输注丙酮酸的早期（闭塞前15分钟）还是晚期（闭塞后3小时）开始，均未改变梗死与危险的关系（对照组：y = 74x - 8.7，r = 0.99；早期输注：y = 0.76x - 9.5，r = 0.85；晚期输注：y = 0.58x - 5.5，r = 0.79）。冠状动脉内给予丙酮酸未能限制梗死面积，这对其在急性心肌缺血情况下的潜在临床效用提出了疑问。
