Dennis S C, Coetzee W A, de Jong J W, Clusin W, Opie L H
Ischemic Heart Disease Research Unit, University of Cape Town Medical School, Observatory, South Africa.
J Pharmacol Exp Ther. 1989 Jan;248(1):372-7.
Although the Ca++ channel blockers can reduce early ischemic ventricular arrhythmias, the mechanisms are unclarified. The antiarrhythmic action of Ca++ antagonists may either be due to vasodilation and negative chronotropism or to trans-sarcolemmal Ca++ influx inhibition. In these studies we investigated the possible individual and additive effects of coronary flow, heart rate and Ca++ antagonism on ventricular arrythmia development in isolated, paced, globally underperfused guinea pig hearts. When the coronary flow during ischemia was raised from 5 to 7% of control and/or the stimulation frequency was decreased from 6 to 4 Hz, ATP and creatine phosphate levels were conserved and intraventricular conduction slowing leading to ventricular tachycardia (VT) was delayed. In contrast, when the coronary flow and pacing rates were fixed at 7% and 6 Hz and diltiazem (10(-6) M) was included in the perfusion medium, there was no effect on tissue high-energy phosphate depletion and development of VT. Even when the breakdown of ATP and the onset of VT were accelerated by isoprenaline (10(-6) M), diltiazem was not antiarrhythmic at this flow rate. Only when the coronary flow was reduced to 5% of control, in the absence and presence of isoprenaline, did diltiazem delay ventricular arrhythmias through a mechanism that was independent of changes in coronary flow and heart rate.
尽管钙离子通道阻滞剂可减少早期缺血性室性心律失常，但其机制尚不清楚。钙离子拮抗剂的抗心律失常作用可能是由于血管舒张和负性变时作用，或者是由于抑制跨肌膜钙离子内流。在这些研究中，我们研究了冠状动脉血流、心率和钙离子拮抗作用对离体、起搏、整体灌注不足的豚鼠心脏室性心律失常发生的可能的个体和相加作用。当缺血期间冠状动脉血流从对照的5%提高到7%和/或刺激频率从6Hz降低到4Hz时，三磷酸腺苷（ATP）和磷酸肌酸水平得以维持，导致室性心动过速（VT）的室内传导减慢被延迟。相比之下，当冠状动脉血流和起搏频率固定在7%和6Hz，且灌注液中加入地尔硫䓬（10⁻⁶M）时，对组织高能磷酸耗竭和室性心动过速的发生没有影响。即使异丙肾上腺素（10⁻⁶M）加速了ATP的分解和室性心动过速的发作，在此血流速率下地尔硫䓬也没有抗心律失常作用。只有当冠状动脉血流降至对照的5%时，无论有无异丙肾上腺素，地尔硫䓬才通过一种独立于冠状动脉血流和心率变化的机制延迟室性心律失常。
