Takeshima S, Vaage J, Valen G
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden.
Acta Physiol Scand. 1997 Nov;161(3):263-70. doi: 10.1046/j.1365-201X.1997.00218.x.
Ischaemic preconditioning has cardioprotective effects. Reactive oxygen species may be possible mediators. The present study investigated whether low doses of exogenous hydrogen peroxide could mimic preconditioning in isolated, Langendorff-perfused rat hearts. Hearts were subjected to two episodes of 3 min global ischaemia and 5 min reperfusion (n = 17), or were given 10 (n = 15), 20 (n = 10), 30 (n = 20), 40 (n = 18), 80 (n = 17) or 160 microM (n = 10) hydrogen peroxide for 10 min, followed by 10 min recovery, before 25 min global ischaemia and 60 min reperfusion, and compared with ischaemic controls of matching perfusion time (n = 17 and n = 23). Cardiac performance was assessed by heart rate, left ventricular systolic, end-diastolic and developed pressures, and coronary flow. Severe reperfusion arrhythmias occurred frequently in control hearts, and was attenuated by ischaemic preconditioning. All hearts pretreated with 160 microM hydrogen peroxide had severe arrhythmias throughout reperfusion, while these were not seen in any heart perfused with 20 microM hydrogen peroxide (P < 0.01 compared to controls). Ischaemia and reperfusion induced a minor decrease in heart rate, left ventricular systolic and developed pressures, and increased end-diastolic pressure. Ischaemic preconditioning attenuated the decrease of heart rate and the increase of end-diastolic pressure, and increased coronary flow, while hydrogen peroxide did not significantly attenuate these changes. In conclusion, a low dose of exogenous hydrogen peroxide before global ischaemia inhibited severe reperfusion arrhythmias, but had no other protective effects. The present work does not suggest that reactive oxygen species are important mediators of the preconditioning effects on stunning and arrhythmias in the rat heart.
缺血预处理具有心脏保护作用。活性氧可能是潜在的介质。本研究调查了低剂量外源性过氧化氢是否能模拟在离体Langendorff灌注大鼠心脏中的预处理。心脏经历两次3分钟全心缺血和5分钟再灌注（n = 17），或给予10（n = 15）、20（n = 10）、30（n = 20）、40（n = 18）、80（n = 17）或160微摩尔（n = 10）过氧化氢10分钟，随后恢复10分钟，然后进行25分钟全心缺血和60分钟再灌注，并与匹配灌注时间的缺血对照组（n = 17和n = 23）进行比较。通过心率、左心室收缩压、舒张末期压和压力升高速率以及冠状动脉血流来评估心脏功能。对照组心脏在再灌注期间频繁出现严重的再灌注心律失常，而缺血预处理可减轻这种情况。所有用160微摩尔过氧化氢预处理的心脏在整个再灌注过程中都出现严重心律失常，而在任何用20微摩尔过氧化氢灌注的心脏中均未观察到这种情况（与对照组相比，P < 0.01）。缺血和再灌注导致心率、左心室收缩压和压力升高速率略有下降，舒张末期压升高。缺血预处理减轻了心率下降和舒张末期压升高，并增加了冠状动脉血流，而过氧化氢并未显著减轻这些变化。总之，在全心缺血前给予低剂量外源性过氧化氢可抑制严重的再灌注心律失常，但没有其他保护作用。目前的研究结果并不表明活性氧是预处理对大鼠心脏顿抑和心律失常作用的重要介质。
