Uematsu M, Okada M
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Jpn J Thorac Cardiovasc Surg. 1998 Sep;46(9):833-45. doi: 10.1007/BF03217831.
It is now well established that pre-treatment with sublethal ischemia, followed by reperfusion, will delay myocardial necrosis during a later sustained ischemic episode, termed ischemic preconditioning (IPC); this has been confirmed experimentally and clinically. However, the effects for the senescent heart differ from those of the mature heart at both functional and cellular levels which have not yet been determined. Comparisons were made between aged (> 135 weeks, n = 18) and mature (15 approximately 20 weeks, n = 8) rabbit hearts which underwent 30 min. normothermic global ischemia with 120 min reperfusion in a buffer-perfused isolated, paced heart model, and the effects of IPC on post-ischemic functional recovery and infarct size were investigated. Ischemic preconditioned hearts (n = 6) were subjected to one cycle of 5 min. global ischemia and 5 min. reperfusion prior to global ischemia. Global ischemic hearts (n = 6) were subjected to 30 min. global ischemia without intervention. Control hearts (n = 6) were subjected to perfusion without ischemia. Post-ischemic functional recovery was better in the ischemic preconditioned hearts than in the global ischemic hearts in both aged and mature hearts. However, in the aged hearts, post-ischemic functional recovery was slightly reduced compared to that of the mature hearts, and only the coronary flow was well-preserved. In the mature hearts, myocardial infarction in the ischemic preconditioned hearts (14.9 +/- 1.3%) and in the control hearts (1.0 +/- 0.3%) was significantly decreased (p < 0.01) compared to that of the global ischemic hearts (32.9 +/- 5.1%). In the aged hearts, myocardial infarction in the ischemic preconditioned hearts (18.9 +/- 2.7%) and in the control hearts (1.1 +/- 0.6%) was significantly decreased (p < 0.001) compared to that of the global ischemic hearts (37.6 +/- 3.7%). The relationship between infarct size and post-ischemic functional recovery of left ventricularpeak developed pressure (LVDP) was linear and the correlation negative, with r = -0.934 (p < 0.001) and -0.875 (p < 0.001) for mature and aged hearts respectively. The data suggest that, in the senescent myocardium, the cellular pathways involved ischemic preconditioning responses that were post-ischemic, and that functional recovery was worse as compared to that of the mature myocardium. Furthermore, the effects of post-ischemic functional recovery became consistently weaker during the control period of 120 min. reperfusion after a prolonged ischemic insult in a buffer perfused isolated rabbit model. However, the effects of infarct size limitation were well-preserved in both senescent and mature myocardia.
现已明确，用亚致死性缺血进行预处理，随后再灌注，会在随后的持续性缺血发作期间延迟心肌坏死，这一现象称为缺血预处理（IPC）；这已在实验和临床中得到证实。然而，衰老心脏的效应在功能和细胞水平上与成熟心脏不同，尚未明确。在一个缓冲液灌注的离体、起搏心脏模型中，对年龄较大（>135周，n = 18）和成熟（约15至20周，n = 8）的兔心脏进行30分钟的常温全心缺血并再灌注120分钟，比较两者情况，并研究IPC对缺血后功能恢复和梗死面积的影响。缺血预处理组心脏（n = 6）在全心缺血前经历一个5分钟全心缺血和5分钟再灌注的周期。全心缺血组心脏（n = 6）接受30分钟全心缺血且无干预。对照组心脏（n = 6）接受无缺血的灌注。在老年和成熟心脏中，缺血预处理组心脏的缺血后功能恢复均优于全心缺血组心脏。然而，在老年心脏中，缺血后功能恢复与成熟心脏相比略有降低，仅冠脉血流得到较好保留。在成熟心脏中，缺血预处理组心脏（14.9±1.3%）和对照组心脏（1.0±0.3%）的心肌梗死与全心缺血组心脏（32.9±5.1%）相比显著降低（p<0.01）。在老年心脏中，缺血预处理组心脏（18.9±2.7%）和对照组心脏（1.1±0.6%）的心肌梗死与全心缺血组心脏（37.6±3.7%）相比显著降低（p<0.001）。梗死面积与左心室峰值收缩压（LVDP）缺血后功能恢复之间的关系呈线性且为负相关，成熟心脏和老年心脏的r值分别为-0.934（p<0.001）和-0.875（p<0.001）。数据表明，在衰老心肌中，参与缺血预处理反应的细胞途径是缺血后反应，且与成熟心肌相比功能恢复较差。此外，在缓冲液灌注的离体兔模型中，长时间缺血损伤后的120分钟再灌注对照期内，缺血后功能恢复的效应持续减弱。然而，梗死面积限制效应在衰老和成熟心肌中均得到较好保留。
