Ciuffo A A, Ouyang P, Becker L C, Levin L, Weisfeldt M L
J Clin Invest. 1985 May;75(5):1504-9. doi: 10.1172/JCI111854.
Eight open chest dogs underwent 25 min of coronary occlusion to determine whether brief myocardial ischemia disrupts the normal myocardial inotropic response to sympathetic nervous stimulation. If so, this could represent a mechanism contributing to postischemic myocardial dysfunction. Myocardial segment shortening was measured using ultrasonic dimension crystals before and after coronary artery occlusion and reperfusion. Left ansa subclavia stimulation and systemic norepinephrine (NE) infusion were used to test the myocardial inotropic response to neural stimulation and direct exposure to the sympathetic mediator, respectively. Before coronary artery occlusion, base-line preischemic segment shortening (12.5 +/- 1.6%) (SEM) increased during both sympathetic stimulation (20.2 +/- 1.4%) and NE infusion (19.7 +/- 1.1%). The control segment responded similarly. After ischemia and reperfusion there was no significant change in heart rate, aortic or left ventricular pressures, nor changes in control segment shortening. In contrast, shortening in the postischemic segment was markedly reduced compared to baseline (4.1 +/- 2.4%), and no longer responded to sympathetic stimulation (2.4 +/- 2.8%), while responsiveness to systemic NE was maintained (12.9 +/- 2.0%), P less than 0.001, which suggested injury to the sympathetic-neural axis during the period of ischemia. This reduced response to neural stimulation was persistent for up to 2 h after reperfusion. Left atrial or intracoronary infusion of bretylium tosylate, which releases norepinephrine from nerve terminals, resulted in an immediate inotropic response in the postischemic segment, which indicated that total depletion of NE from nerve terminals during the ischemic period had not occurred. Disruption of sympathetic neural responsiveness is likely a component of the mechanism of postischemic myocardial dysfunction whenever there is appreciable sympathetic drive to the heart.
八只开胸犬经历了25分钟的冠状动脉闭塞，以确定短暂的心肌缺血是否会破坏心肌对交感神经刺激的正常变力反应。如果是这样，这可能代表了一种导致缺血后心肌功能障碍的机制。在冠状动脉闭塞和再灌注前后，使用超声尺寸晶体测量心肌节段缩短。分别使用左锁骨下襻刺激和全身去甲肾上腺素（NE）输注来测试心肌对神经刺激和直接暴露于交感介质的变力反应。在冠状动脉闭塞前，基线缺血前节段缩短（12.5±1.6%）（标准误）在交感刺激（20.2±1.4%）和NE输注（19.7±1.1%）期间均增加。对照节段反应相似。缺血和再灌注后，心率、主动脉或左心室压力无显著变化，对照节段缩短也无变化。相比之下，缺血后节段的缩短与基线相比明显减少（4.1±2.4%），不再对交感刺激作出反应（2.4±2.8%），而对全身NE的反应性得以维持（12.9±2.0%），P<0.001，这表明在缺血期间交感神经轴受到损伤。这种对神经刺激的反应降低在再灌注后持续长达2小时。左心房或冠状动脉内输注托西溴苄铵，从神经末梢释放去甲肾上腺素，导致缺血后节段立即出现变力反应，这表明在缺血期间神经末梢的NE并未完全耗尽。只要心脏有明显的交感驱动，交感神经反应性的破坏很可能是缺血后心肌功能障碍机制的一个组成部分。
