Aiello E A, Jabr R I, Cole W C
Department of Pharmacology and Therapeutics, University of Calgary, Alberta, Canada.
Circ Res. 1995 Jul;77(1):153-62. doi: 10.1161/01.res.77.1.153.
The role of reactive metabolites of oxygen, oxygen radicals (O-Rs), as mediators of potentially arrhythmogenic alterations in cellular electrical properties and contractile dysfunction of cardiac muscle during reperfusion after ischemia was investigated. Electrical and mechanical activities of arterially perfused guinea pig right ventricular walls were recorded simultaneously with intracellular microelectrodes and a force transducer. Preparations were maintained in Krebs-Henseleit solution (perfusion rate, 1.5 mL/min) and subjected to 30 minutes of no-flow ischemia followed by 60 minutes of reperfusion or pretreated with O-R scavengers (superoxide dismutase, 50 U/mL; catalase, 600 U/mL; and mannitol, 2 mmol/L) for 10 to 20 minutes, followed by 30 minutes of ischemia and 60 minutes of reperfusion. Reperfusion in untreated preparations caused (1) depolarization of resting membrane potential by 8 to 10 mV and slow recovery of action potential duration requiring 60 minutes to attain the preischemic duration, (2) tachyarrhythmias and premature action potentials, (3) postischemic contractile dysfunction, and (4) increased coronary perfusion pressure in untreated preparations. Pretreatment with scavenger cocktail affected neither electrical nor contractile activity before or during no-flow ischemia, but it (1) accelerated recovery of resting membrane potential and action potential duration, (2) reduced the incidence of tachyarrhythmia, (3) improved contractile function, and (4) inhibited the rise in perfusion pressure on reflow. Reperfusion with an exogenous O-R-generating system containing xanthine/xanthine oxidase (X/XO, 2 mmol/L:10 mU/mL) inhibited recovery of action potential duration and contractility. Treatment of normoxic arterially perfused right ventricular walls with X/XO caused a decline in action potential duration by approximately 20% within 30 minutes. In contrast, X/XO caused a 30% increase in the duration of action potentials in superfused papillary muscles or small strips of right ventricular walls over the same time period. Pretreatment with sodium nitroprusside (10 mumol/L) inhibited the decline in duration induced by X/XO in normoxic right ventricular walls but was without effect on prolongation due to X/XO in papillary muscles. Reperfusion with nitroprusside after no-flow ischemia caused (1) accelerated recovery of preischemic action potential configuration, (2) a significant decline in the incidence of reperfusion arrhythmias, (3) improved postischemic contractile performance, and (4) inhibition of the increase in perfusion pressure associated with reflow. The data indicate that slow recovery of the action potential duration caused by O-Rs in reperfusion cannot be explained by the direct effects of O-Rs on cardiac myocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
研究了氧的反应性代谢产物——氧自由基（O-Rs）在心肌缺血后再灌注期间作为细胞电特性潜在致心律失常改变和心肌收缩功能障碍介质的作用。用细胞内微电极和力传感器同时记录豚鼠动脉灌注右心室壁的电活动和机械活动。将标本置于 Krebs-Henseleit 溶液中（灌注速率为 1.5 mL/min），进行 30 分钟无血流缺血，随后再灌注 60 分钟，或先用 O-R 清除剂（超氧化物歧化酶，50 U/mL；过氧化氢酶，600 U/mL；甘露醇，2 mmol/L）预处理 10 至 20 分钟，然后进行 30 分钟缺血和 60 分钟再灌注。未处理标本的再灌注导致：（1）静息膜电位去极化 8 至 10 mV，动作电位持续时间缓慢恢复，需 60 分钟才能达到缺血前持续时间；（2）快速性心律失常和早搏动作电位；（3）缺血后收缩功能障碍；（4）未处理标本中冠状动脉灌注压升高。用清除剂混合物预处理在无血流缺血前或期间对电活动和收缩活动均无影响，但它（1）加速了静息膜电位和动作电位持续时间的恢复；（2）降低了快速性心律失常的发生率；（3）改善了收缩功能；（4）抑制了再灌注时灌注压的升高。用含有黄嘌呤/黄嘌呤氧化酶（X/XO，2 mmol/L:10 mU/mL）的外源性 O-R 生成系统进行再灌注抑制了动作电位持续时间和收缩力的恢复。用 X/XO 处理常氧动脉灌注的右心室壁，30 分钟内动作电位持续时间下降约 20%。相比之下，在相同时间段内，X/XO 使 superfused 乳头肌或右心室壁小条带的动作电位持续时间增加 30%。用硝普钠（10 μmol/L）预处理可抑制 X/XO 诱导的常氧右心室壁动作电位持续时间的下降，但对乳头肌中 X/XO 所致的延长无影响。无血流缺血后用硝普钠进行再灌注导致：（1）缺血前动作电位形态的恢复加速；（2）再灌注心律失常的发生率显著下降；（3）缺血后收缩性能改善；（4）抑制了与再灌注相关的灌注压升高。数据表明，再灌注时 O-Rs 导致的动作电位持续时间缓慢恢复不能用 O-Rs 对心肌细胞的直接作用来解释。（摘要截短至 400 字）
