Sakamoto J, Miura T, Tsuchida A, Fukuma T, Hasegawa T, Shimamoto K
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Basic Res Cardiol. 1999 Dec;94(6):489-95. doi: 10.1007/s003950050165.
In this study, we examined the features of reperfusion arrhythmias and the effect of preconditioning (PC) in the mouse for future application of genetically engineered mice to study mechanisms of this type of arrhythmia. Under pentobarbital anesthesia, reperfusion arrhythmias were induced by temporary occlusion of the left anterior descending coronary artery and reperfusion in BALB/c AJc1 mice. In the first protocol, the coronary artery was occluded for periods ranging from 2 to 15 min and then reperfused. In the second protocol, hearts were preconditioned with 2- or 3-min ischemia and 5-min reperfusion prior to the 5 min of coronary occlusion. An electrocardiogram was recorded throughout the experiment, and arrhythmias were diagnosed according to the Lambeth Convention criteria. The incidences of reperfusion-induced ventricular tachycardia (VT) in hearts that received 2, 3, 5, 10 and 15-min ischemia (n = 10 approximately 14) were 0, 9, 73, 55 and 30 %, respectively. Ventricular fibrillation (VF) was not observed upon reperfusion regardless of the ischemia duration. PC with 2-min ischemia and with 3-min ischemia (n = 10 for each PC) reduced the incidences of reperfusion VT after 5-min ischemia to 40% and 10%, respectively. However, in mice that developed reperfusion VT, the VT duration was similar to that in non-preconditioned controls, ranging from 1 to 16 s. These results suggest that the relationship between ischemia duration and incidence of VT upon subsequent reperfusion is "bell shaped" and that PC has anti-arrhythmic effects in the mouse, as it does in anesthetized rat hearts. However, there appear to be differences in the incidence of reperfusion-induced VF and the duration of reperfusion VT between these species. Thus, the present murine preparation appears to be a useful model for studying the mechanism of reperfusion VT and PC, though it does not share all of the features of reperfusion arrhythmias with the anesthetized rat preparation.
在本研究中,我们研究了再灌注性心律失常的特征以及预处理(PC)对小鼠的影响,以便未来将基因工程小鼠应用于研究此类心律失常的机制。在戊巴比妥麻醉下,通过暂时阻断左冠状动脉前降支并在BALB/c AJc1小鼠中进行再灌注来诱发再灌注性心律失常。在第一个方案中,冠状动脉阻断2至15分钟,然后再灌注。在第二个方案中,在冠状动脉阻断5分钟之前,心脏先进行2或3分钟的缺血和5分钟的再灌注预处理。在整个实验过程中记录心电图,并根据兰贝斯会议标准诊断心律失常。接受2、3、5、10和15分钟缺血(n = 10至14)的心脏中,再灌注诱发室性心动过速(VT)的发生率分别为0、9、73、55和30%。无论缺血持续时间如何,再灌注时均未观察到心室颤动(VF)。2分钟缺血和3分钟缺血预处理(每种预处理n = 10)分别将5分钟缺血后再灌注VT的发生率降低至40%和10%。然而,在发生再灌注VT的小鼠中,VT持续时间与未预处理的对照组相似,为1至16秒。这些结果表明,缺血持续时间与随后再灌注时VT发生率之间的关系呈“钟形”,并且PC在小鼠中具有抗心律失常作用,就像在麻醉大鼠心脏中一样。然而,这些物种之间在再灌注诱发VF的发生率和再灌注VT的持续时间方面似乎存在差异。因此,目前的小鼠制备似乎是研究再灌注VT机制和PC的有用模型,尽管它并不具备与麻醉大鼠制备相同的所有再灌注性心律失常特征。