Limbruno U, Zucchi R, Ronca-Testoni S, Galbani P, Ronca G, Mariani M
Institute of Cardiology, University of Pisa, Italy.
J Mol Cell Cardiol. 1989 Oct;21(10):1063-72. doi: 10.1016/0022-2828(89)90804-3.
Transient ischemia does not induce myocardial necrosis but may be associated with prolonged contractile dysfunction ("stunned" myocardium). It has been suggested that alteration of the excitation-contraction coupling system (sarcoplasmic reticulum) could be responsible for this phenomenon. We tested this hypothesis by characterizing sarcoplasmic reticulum (SR) function in an isolated rat heart model of "stunned" myocardium (hearts reperfused after 10 min of normothermic global ischemia). At the end of the ischemic period oxalate-supported Ca-uptake was depressed either in the whole homogenate or in isolated SR (to 47% and 22% of control values, respectively). During reperfusion Ca-uptake of the whole heart homogenate recovered almost completely whereas slight but significant depression persisted in isolated SR (48 +/- 2 vs 67 +/- 4 nmol/min x mg, P less than 0.01). In the presence of ruthenium red or ryanodine, two inhibitors of SR Ca-release channels, Ca-uptake was stimulated. Both in the whole heart homogenate and in isolated SR, such stimulation was remarkably smaller after reperfusion than in control conditions (P less than 0.001) suggesting reduced conductivity state of the SR Ca-release channels. Ca-stimulated, magnesium-dependent ATPase activity was remarkably reduced during ischemia and postischemic reperfusion induced only incomplete recovery (93 +/- 18 vs 169 +/- 14 nmol ATP/min x mg protein, P less than 0.05). We conclude that complex modifications of SR function occur in the "stunned" myocardium and could contribute to the contractile impairment found in this condition.
短暂性缺血不会诱发心肌坏死，但可能与收缩功能障碍持续时间延长（“顿抑”心肌）有关。有人提出，兴奋 - 收缩偶联系统（肌浆网）的改变可能是这种现象的原因。我们通过在“顿抑”心肌的离体大鼠心脏模型（常温全心缺血10分钟后再灌注的心脏）中表征肌浆网（SR）功能来检验这一假设。在缺血期末，草酸盐支持的钙摄取在全匀浆或分离的SR中均降低（分别降至对照值的47%和22%）。在再灌注期间，全心匀浆的钙摄取几乎完全恢复，而分离的SR中仍存在轻微但显著的降低（48±2对67±4 nmol/分钟×毫克，P<0.01）。在存在钌红或兰尼碱这两种SR钙释放通道抑制剂的情况下，钙摄取受到刺激。在全心匀浆和分离的SR中，再灌注后的这种刺激均明显小于对照条件下（P<0.001），表明SR钙释放通道的传导状态降低。钙刺激的、镁依赖性ATP酶活性在缺血期间显著降低，缺血后再灌注仅诱导不完全恢复（93±18对169±14 nmol ATP/分钟×毫克蛋白质，P<0.05）。我们得出结论，“顿抑”心肌中发生了SR功能的复杂改变，这可能导致了这种情况下发现的收缩功能损害。
