Baxter G F, Yellon D M
Department of Pharmacology, De Montfort University, Leicester, UK.
Cardiovasc Drugs Ther. 1993 Apr;7(2):225-31. doi: 10.1007/BF00878512.
The ability of the calcium antagonist diltiazem to protect against reperfusion-induced arrhythmias in hypertrophied myocardium was studied. Hearts from normotensive and DOCA-salt hypertensive rats were Langendorff perfused and subjected to 10 minutes of stabilization, 10 minutes of left coronary artery occlusion, and 5 minutes of reperfusion. The incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) during reperfusion were determined and the effects of diltiazem or vehicle (given as a single bolus 3 minutes before coronary artery occlusion) were assessed in hypertrophied and normal hearts. In vehicle-treated (control) hypertrophied hearts, VF incidence was 91% compared with 67% in normal hearts, and the median duration of VF was 272 seconds (mean 207.4 +/- 32.3) compared with 27 seconds (mean 110.6 +/- 36.6; p < 0.05), respectively, suggesting that reperfusion VF is more severe in hypertrophied hearts. In normal hearts, diltiazem 18 micrograms reduced VT incidence from 92% to 55%, reduced VF from 67% to 27%, and sustained VF from 42% to 9%. In hypertrophied hearts, 18 micrograms diltiazem reduced the VT incidence from 100% to 58%, reduced VF from 91% to 25% (p < 0.01), and sustained VF from 82% to 8% (p < 0.01). Median VF duration in this group was reduced to 0 seconds (p < 0.05; mean 24.7 +/- 22.6). Diltiazem did not significantly affect heart rate or coronary flow rate decreases during ischemia. However, developed tension, at the onset of ischemia, was lower in diltiazem-treated groups than in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了钙拮抗剂地尔硫䓬对肥厚心肌再灌注诱导的心律失常的保护作用。将正常血压大鼠和去氧皮质酮盐高血压大鼠的心脏进行Langendorff灌注,并进行10分钟的稳定期、10分钟的左冠状动脉阻塞和5分钟的再灌注。测定再灌注期间室性心动过速(VT)和室性颤动(VF)的发生率和持续时间,并评估地尔硫䓬或赋形剂(在冠状动脉阻塞前3分钟单次推注)对肥厚心脏和正常心脏的影响。在接受赋形剂治疗(对照)的肥厚心脏中,VF发生率为91%,而正常心脏中为67%,VF的中位持续时间分别为272秒(平均207.4±32.3)和27秒(平均110.6±36.6;p<0.05),表明再灌注VF在肥厚心脏中更严重。在正常心脏中,18微克地尔硫䓬使VT发生率从92%降至55%,VF从67%降至27%,持续性VF从42%降至9%。在肥厚心脏中,18微克地尔硫䓬使VT发生率从100%降至58%,VF从91%降至25%(p<0.01),持续性VF从82%降至8%(p<0.01)。该组VF的中位持续时间降至0秒(p<0.05;平均24.7±22.6)。地尔硫䓬对缺血期间的心率或冠状动脉血流速度降低没有显著影响。然而,在缺血开始时,地尔硫䓬治疗组的心肌张力低于对照组。(摘要截断于250字)