Thandroyen F T, McCarthy J, Burton K P, Opie L H
Department of Medicine, University of Cape Town, South Africa.
Circ Res. 1988 Feb;62(2):306-14. doi: 10.1161/01.res.62.2.306.
This study investigates the possible role of oscillatory release of calcium from sarcoplasmic reticulum in the genesis of ventricular arrhythmias during acute myocardial ischemia and reperfusion in isolated rat hearts. We used ryanodine and caffeine, which are known to modulate the oscillatory release of calcium from sarcoplasmic reticulum. During 30 minutes of left main coronary artery ligation, all 13 control hearts developed ventricular premature beats (number of beats, 225 +/- 51) and ventricular tachycardia (duration, 123 +/- 21 seconds); five hearts developed ventricular fibrillation. In a separate series of experiments, reperfusion after 15 minutes of coronary artery ligation caused ventricular fibrillation to occur within 15 seconds in all 12 hearts. Ryanodine (10(-9) to 10(-7) M) abolished ventricular arrhythmias during coronary artery ligation and prevented reperfusion ventricular fibrillation. Ryanodine (10(-9), 10(-8), and 10(-7) M) caused 15%, 23%, and 74% decreases in the maximal rate of rise of left ventricular pressure development and 20%, 32%, and 85% decreases in the maximal rate of fall of left ventricular pressure development, respectively, prior to coronary artery ligation. During acute myocardial ischemia, ryanodine 10(-9) M maintained and 10(-8) M impaired left ventricular function; 10(-7) M caused left ventricular failure. Coronary perfusion rate did not increase during ischemia. Antiarrhythmic activity occurred independent of preservation of high energy phosphates, reduction in tissue lactate, or tissue cyclic adenosine monophosphate in the ischemic myocardium. Caffeine 10(2) M decreased the incidence of ventricular arrhythmias during ischemia and upon reperfusion; protection occurred coincident with development of diastolic contracture. Caffeine increased ischemic tissue cyclic adenosine monophosphate content and worsened tissue energy status.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究调查了在离体大鼠心脏急性心肌缺血和再灌注期间，肌浆网钙振荡释放在心性心律失常发生过程中可能发挥的作用。我们使用了已知可调节肌浆网钙振荡释放的兰尼碱和咖啡因。在左冠状动脉主干结扎30分钟期间，所有13颗对照心脏均出现室性早搏（早搏次数为225±51次）和室性心动过速（持续时间为123±21秒）；5颗心脏发生心室颤动。在另一系列实验中，冠状动脉结扎15分钟后再灌注，所有12颗心脏均在15秒内发生心室颤动。兰尼碱（10⁻⁹至10⁻⁷M）可消除冠状动脉结扎期间的室性心律失常，并预防再灌注性心室颤动。在冠状动脉结扎前，兰尼碱（10⁻⁹、10⁻⁸和10⁻⁷M）分别使左心室压力上升最大速率降低15%、23%和74%，使左心室压力下降最大速率降低20%、32%和85%。在急性心肌缺血期间，10⁻⁹M兰尼碱维持左心室功能，10⁻⁸M损害左心室功能；10⁻⁷M导致左心室衰竭。缺血期间冠状动脉灌注率未增加。抗心律失常活性的发生与缺血心肌中高能磷酸盐的保存、组织乳酸的减少或组织环磷酸腺苷无关。10²M咖啡因可降低缺血期间和再灌注时室性心律失常的发生率；保护作用与舒张期挛缩的发生同时出现。咖啡因增加了缺血组织环磷酸腺苷含量，并使组织能量状态恶化。（摘要截断于250字）
