Offstad J, Sommerschild H, Ilebekk A, Kirkebøen K A, Downing S E
Institute for Experimental Medical Research, University of Oslo, Oslo, Norway.
J Mol Cell Cardiol. 1997 Nov;29(11):2997-3007. doi: 10.1006/jmcc.1997.0505.
Myocardial infarction appears after 20 min of regional no-flow ischemia in vivo, but only after a much longer duration of global ischemia in isolated hearts. We tested whether repetitive myocardial stretching (RMS), as occurs in segmental ischemia, is involved in the pathogenesis of myocardial cell injury. Furthermore, we evaluated the role of stretch-activated channels by using Gadolinium (Gd3+). Isolated piglet hearts were perfused with red cell enriched Krebs-Henseleit buffer. RMS was induced by inflating a balloon in the left ventricle, using a control system to provide a pressure of 120 mmHg during one-third of the cycle and 0 mmHg during the rest of the cycle, with a frequency 150 per min. Function and metabolism were compared during 2 h of low-flow ischemia (10% of control), with and without RMS, followed by 1 h of reperfusion. Non-RMS hearts were exposed to saline (Isch), or Gd3+ 25 micromol/l (Gd3+-Isch). During ischemia, left ventricular systolic pressure (LVSP) stabilized in non-RMS hearts, but a further decrease, combined with increased anaerobic metabolism occurred in RMS hearts. After 30 min of reperfusion in the non-stretched hearts, LVSP returned to 77+/-4% of control (mean+/-s.e.) in the Isch group, and to 74+/-2% in the Gd3+-isch group (between groups; P=n.s.). In hearts exposed to RMS, LVSP returned to only 46+/-4% of control (RMS) and to 51+/-3% in the Gd3+-RMS group (both P=0.01 v Isch). The same alterations were seen for LV dP/dt. In RMS hearts, tissue concentrations of ATP were reduced and concentrations of lactate increased. We conclude that stretching of ischemic myocardium severely increases anaerobic metabolism and reduces functional and metabolic recovery. Blockade of stretch activated channels by Gd3+ does not prevent this effect. Thus, the reduced recovery induced by RMS is due to factors other than ion fluxes through stretch-activated channels.
在体内，局部无血流缺血20分钟后会出现心肌梗死，但在离体心脏中，只有在更长时间的全心缺血后才会出现。我们测试了节段性缺血时发生的重复性心肌拉伸（RMS）是否参与心肌细胞损伤的发病机制。此外，我们通过使用钆（Gd3+）评估了牵张激活通道的作用。用富含红细胞的Krebs-Henseleit缓冲液灌注离体仔猪心脏。通过在左心室内充气球囊诱导RMS，使用控制系统在心动周期的三分之一时间内提供120 mmHg的压力，在心动周期的其余时间内提供0 mmHg的压力，频率为每分钟150次。在低血流缺血（为对照的10%）2小时期间，比较有和没有RMS情况下的心脏功能和代谢，随后进行1小时的再灌注。未进行RMS的心脏暴露于生理盐水（缺血组）或25 μmol/l的Gd3+（Gd3+-缺血组）中。在缺血期间，未进行RMS的心脏左心室收缩压（LVSP）稳定，但进行RMS的心脏LVSP进一步下降，同时无氧代谢增加。在未拉伸的心脏再灌注30分钟后，缺血组LVSP恢复到对照值的77±4%（平均值±标准误），Gd3+-缺血组恢复到74±2%（两组间；P=无显著差异）。在进行RMS的心脏中，LVSP仅恢复到对照值的46±4%（RMS组），在Gd3+-RMS组中恢复到51±3%（两者与缺血组相比，P=0.01）。左心室dp/dt也出现了相同的变化。在进行RMS的心脏中，ATP的组织浓度降低，乳酸浓度增加。我们得出结论，缺血心肌的拉伸会严重增加无氧代谢，并降低功能和代谢恢复。Gd3+阻断牵张激活通道并不能防止这种效应。因此，RMS导致的恢复降低是由于除通过牵张激活通道的离子通量之外的其他因素。
