Adachi T, Miura T, Suzuki K, Iimura O
Second Department of Internal Medicine Sapporo Medical University, School of Medicine, Japan.
Basic Res Cardiol. 1994 Jan-Feb;89(1):16-28. doi: 10.1007/BF00788674.
The role of free radicals and the protective action of calcium antagonists have been established in myocardial stunning in canine hearts, which contain a considerable level of xanthine oxidase, a free radical producing enzyme. However, myocardial stunning in hearts which lack xanthine oxidase and its modification by calcium antagonists in vivo remain uncharacterized. The present study examined this issue using open-chest anesthetized rabbits. Myocardial stunning was induced by a 10-min coronary occlusion and reperfusion. Regional systolic thickening fraction (TF) was determined using an epicardial Doppler sensor, together with other hemodynamic parameters. In untreated control rabbits, recovery of TF from the 10 min transient ischemia was 43 +/- 3% of the baseline at 30 min after reperfusion. Administration of verapamil (200 micrograms/kg bolus plus 40 micrograms/kg/min), which was started before the onset of ischemia and continued until 20 min after reperfusion, significantly improved the recovery of TF to 74 +/- 6% (p < 0.05). A similar improvement in post-ischemic contractile function (TF = 77 +/- 10%) was observed when verapamil was injected at the same rate, but the infusion was discontinued 1 min after the coronary occlusion. Myocardial ATP depletion after the 10 min ischemia was significantly less in the verapamil-pretreated rabbits compared with untreated controls (10.1 +/- 1.0 vs. 6.2 +/- 0.7 mumol/g dry wt., p < 0.05). The difference in TF between the rabbit with and without verapamil treatment could not be explained by afterload reduction. When verapamil (100 micrograms/kg bolus plus 20 micrograms/kg/min) was given during the reperfusion period alone, TF recovery was poorer (TF = 22 +/- 8%) than the control value. Thus, it was concluded that verapamil attenuates myocardial stunning in the hearts with trace levels of xanthine oxidase, and that the beneficial effect is achieved only by pretreatment, not by post-ischemic treatment with verapamil.
自由基的作用以及钙拮抗剂的保护作用已在犬心脏的心肌顿抑中得到证实，犬心脏含有相当水平的黄嘌呤氧化酶，这是一种产生自由基的酶。然而，缺乏黄嘌呤氧化酶的心脏中的心肌顿抑及其在体内被钙拮抗剂修饰的情况仍未明确。本研究使用开胸麻醉兔对此问题进行了研究。通过10分钟的冠状动脉闭塞和再灌注诱导心肌顿抑。使用心外膜多普勒传感器测定区域收缩增厚分数（TF）以及其他血流动力学参数。在未经治疗的对照兔中，再灌注30分钟时，TF从10分钟短暂缺血中的恢复为基线的43±3%。在缺血开始前开始给予维拉帕米（200微克/千克推注加40微克/千克/分钟）并持续至再灌注后20分钟，显著改善了TF的恢复，使其达到74±6%（p<0.05）。当以相同速率注射维拉帕米，但在冠状动脉闭塞后1分钟停止输注时，观察到缺血后收缩功能有类似改善（TF = 77±10%）。与未治疗的对照相比，维拉帕米预处理的兔在10分钟缺血后的心肌ATP消耗明显减少（10.1±1.0对6.2±0.7微摩尔/克干重，p<0.05）。有或没有维拉帕米治疗的兔之间TF的差异不能用后负荷降低来解释。当仅在再灌注期间给予维拉帕米（100微克/千克推注加20微克/千克/分钟）时，TF恢复比对照值更差（TF = 22±8%）。因此，得出结论，维拉帕米可减轻黄嘌呤氧化酶水平微量的心脏中的心肌顿抑，并且有益效果仅通过预处理实现，而不是通过缺血后用维拉帕米治疗实现。
