Priori S G, Zuanetti G, Schwartz P J
Unità di Studio delle Aritmie, Ospedale Maggiore, Milano, Italy.
Am Heart J. 1988 Jul;116(1 Pt 1):37-43. doi: 10.1016/0002-8703(88)90247-5.
Sympathetic hyperactivity plays a major role in the genesis of malignant arrhythmias during acute myocardial ischemia. An experimental model in which life-threatening arrhythmias are specifically and consistently induced by the interaction between acute myocardial ischemia and left stellate ganglion stimulation has been developed in alpha-chloralose anesthetized cats. In this preparation, drugs that share antiischemic, antiadrenergic, and specific electrophysiologic effects, such as verapamil, diltiazem, and amiodarone, were most effective. To evaluate the relative role of these different properties in mediating the effect of antiarrhythmic drugs, we used this same model to test nifedipine, a calcium channel blocker that is able to counteract the consequences of sympathetic stimulation on coronary circulation but has no electrophysiologic properties at concentrations relevant in the clinical setting. Nifedipine (15 micrograms/kg) prevented the occurrence of ventricular fibrillation in 10 of 13 animals (77%). Its efficacy was independent of changes in the peripheral hemodynamics. Plasma concentrations of nifedipine were within the therapeutic range in humans. To evaluate if this rather striking protective effect was specifically related to the prevention of the deleterious consequences of sympathetic stimulation, the effect of nifedipine on ventricular fibrillation threshold was studied in an additional group of 13 cats in the nonischemic state, during acute myocardial ischemia and during ischemia plus sympathetic stimulation. Nifedipine did not modify ventricular fibrillation threshold in nonischemic or in ischemic conditions. However, nifedipine specifically prevented the further reduction in ventricular fibrillation threshold occurring when sympathetic stimulation was superimposed on acute ischemia. These data suggest that the extension of ischemic damage by sympathetic stimulation is an important progenitor of arrhythmogenic action during acute ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
交感神经过度兴奋在急性心肌缺血期间恶性心律失常的发生中起主要作用。在α-氯醛糖麻醉的猫中建立了一种实验模型，在该模型中，急性心肌缺血与左星状神经节刺激之间的相互作用可特异性且持续地诱发危及生命的心律失常。在该实验准备中，具有抗缺血、抗肾上腺素能和特定电生理作用的药物，如维拉帕米、地尔硫䓬和胺碘酮，效果最为显著。为了评估这些不同特性在介导抗心律失常药物作用中的相对作用，我们使用相同的模型来测试硝苯地平，一种钙通道阻滞剂，它能够抵消交感神经刺激对冠状动脉循环的影响，但在临床相关浓度下没有电生理特性。硝苯地平（15微克/千克）可预防13只动物中的10只（77%）发生心室颤动。其疗效与外周血流动力学的变化无关。硝苯地平的血浆浓度在人类治疗范围内。为了评估这种相当显著的保护作用是否与预防交感神经刺激的有害后果特别相关，在另一组13只非缺血状态、急性心肌缺血期间以及缺血加交感神经刺激期间的猫中研究了硝苯地平对心室颤动阈值的影响。硝苯地平在非缺血或缺血条件下均未改变心室颤动阈值。然而，硝苯地平特异性地预防了在急性缺血基础上叠加交感神经刺激时心室颤动阈值的进一步降低。这些数据表明，交感神经刺激导致的缺血损伤扩展是急性缺血期间致心律失常作用的一个重要根源。（摘要截短至250字）
