Hearse D J, Tosaki A
Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London, UK.
J Mol Cell Cardiol. 1988 Mar;20(3):213-23. doi: 10.1016/s0022-2828(88)80054-3.
Using the isolated perfused rat heart with regional ischemia and reperfusion, we have two antiarrhythmic interventions (the spin trap agent PBN [N-tert-butyl-alpha-phenylnitrone] and perfusate calcium reduction), administered just before reperfusion, to investigate mechanisms determining the vulnerability of the heart to reperfusion-induced ventricular fibrillation. Hearts were subjected to regional ischemia (5, 10, 20, 30 or 40 min) followed by reperfusion. Four groups were studied for each ischemic time: (i) control hearts with no antiarrhythmic intervention; (ii) hearts perfused with PBN (30 mumol/l) during the final 1 min of ischemia and throughout reperfusion, (iii) hearts perfused with low-calcium buffer (0.4 mmol/l) during the final 1 min of ischemia and throughout reperfusion and (iv) hearts perfused with PBN (30 mumol/l) and low-calcium (0.4 mmol/l) during the final 1 min of ischemia and throughout reperfusion. In control hearts, a bell-shaped time-vulnerability curve was obtained with 0, 91, 67, 33 and 17% of the hearts exhibiting irreversible fibrillation during reperfusion after 5, 10, 20, 30 and 40 min of ischemia, respectively. In the PBN group, the values were 8, 41 (P less than 0.05), 41, 33 and 8%, respectively. In the calcium reduction group the values were 17, 50, 8 (P less than 0.05), 8 and 0, respectively. Thus, PBN caused a significant reduction in reperfusion-induced ventricular fibrillation after 10 min of ischemia but had no significant effect with reperfusion after 20 min of ischemia. In contrast, calcium reduction had no significant effect after 10 min of ischemia but caused a significant reduction after 20 min of ischemia. When PBN treatment with calcium reduction were combined we obtained significant anti-arrhythmic effects after both 10 min (P less than 0.05) and 20 min (P less than 0.05) of ischemia. The additive effects of these two interventions, and the different ischemic-times after which they are most effective, has led us to propose that multiple triggers, each with different underlying mechanisms may be capable of initiating events which lead to ventricular fibrillation.
利用分离的灌注大鼠心脏进行局部缺血和再灌注实验，我们在再灌注前实施了两种抗心律失常干预措施（自旋捕捉剂PBN [N-叔丁基-α-苯基硝酮] 和降低灌注液中的钙浓度），以研究决定心脏对再灌注诱导的心室颤动易感性的机制。心脏先经历局部缺血（5、10、20、30或40分钟），然后进行再灌注。对于每个缺血时间，研究了四组：（i）未进行抗心律失常干预的对照心脏；（ii）在缺血的最后1分钟及整个再灌注过程中用PBN（30 μmol/L）灌注的心脏；（iii）在缺血的最后1分钟及整个再灌注过程中用低钙缓冲液（0.4 mmol/L）灌注的心脏；（iv）在缺血的最后1分钟及整个再灌注过程中用PBN（30 μmol/L）和低钙（0.4 mmol/L）灌注的心脏。在对照心脏中，获得了一条钟形的时间易感性曲线，在缺血5、10、20、30和40分钟后再灌注期间，分别有0、91、67、33和17%的心脏出现不可逆性颤动。在PBN组中，相应的值分别为8、41（P<0.05）、41、33和8%。在降低钙浓度组中，相应的值分别为17、50、8（P<0.05）、8和0。因此，PBN在缺血10分钟后能显著降低再灌注诱导的心室颤动，但在缺血20分钟后再灌注时无显著作用。相反，降低钙浓度在缺血10分钟后无显著作用，但在缺血20分钟后能显著降低心室颤动。当PBN治疗与降低钙浓度联合使用时，在缺血10分钟（P<0.05）和20分钟（P<0.05）后均获得了显著的抗心律失常效果。这两种干预措施的相加作用以及它们最有效的不同缺血时间，使我们提出多个触发因素，每个因素都有不同的潜在机制，可能能够引发导致心室颤动的事件。
