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Nonlinear dynamics of heart beat rhythm during ischemia / reperfusion and death of cardiac myocytes.

心肌细胞缺血/再灌注和死亡期间心跳节律的非线性动力学。

基本信息

批准号：
10480240
负责人：
KAWAHARA Koichi
金额：
$ 6.46万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10480240/
关键词：
ischemia reperfusion cardiac myocyte beating rhythm myocyte death

项目摘要

Cardiomyocyte apoptosis has been demonstrated in animal models of ischemia/reperfusion injury as well as patients with congestive heart failure or acute myocardial infarction. However, the mechanism responsible for cardiomyocyte apoptosis remains largely unknown. The present study aimed at elucidating the mechanisms responsible for the induction of cardiac arrhythmia associated with ischemia/reperfusion cardiac injury. The results obtained from this study are summarized as follows:(1) In the cultured dissociated myocytes from neonatal rats, inhibition of de novo protein synthesis itself by cycloheximide (CHX) evoked myocyte-specific apoptosis-like cell death. CHX-induced myocyte death was reduced by a treatment with a cell-permeable, specific inhibitor of caspase-3 (CPP32). Reactive oxygen Species (ROS) appeared to be involved in the CHX-induced myocyte death, because such cell death was prevented by co-treatment of Mn(III) tetrakis(benzoic acid) porphyrin (MnTBAP), a cell-permeable superoxide dismutase mimic. Our results suggest a possibility that cardiomyocyte apoptosis would not require de novo protein synthesis, and that protein synthesis inhibition itself would result in the myocyte apoptosis.(2) In the cultured dissociated myocytes from neonatal rats, hypoxia and glucose deprivation (in vitro ischemia) resulted in the increase of the contraction interval and of the fluctuation of the beating rhythm. However, synchronization between myocytes remained unchanged during in vitro ischemia. This result suggests a possibility that gap-junction among myocytes remained open during hypoxia/ischemla.(3) In the Langendorff-perfused heart from adult rats, global ischemia resulted in the elongation of heart periods, and the heart eventually stopped beating in about 10 min. However, heart beat rhythm recovered to the control one after reperfusion in most of the Langendorff preparations. In some cases, reperfusion induced arrhythmia-like irregular beat.

心肌细胞凋亡已在缺血/再灌注损伤的动物模型以及充血性心力衰竭或急性心肌梗塞患者中得到证实。然而，心肌细胞凋亡的机制仍然很大程度上未知。本研究旨在阐明诱发与缺血/再灌注心脏损伤相关的心律失常的机制。本研究的结果概括如下：(1)在培养的新生大鼠离体肌细胞中，放线菌酮(CHX)抑制蛋白质从头合成本身，引起肌细胞特异性凋亡样细胞死亡。通过细胞渗透性特异性 caspase-3 (CPP32) 抑制剂治疗可减少 CHX 诱导的心肌细胞死亡。活性氧 (ROS) 似乎参与了 CHX 诱导的心肌细胞死亡，因为这种细胞死亡可以通过细胞渗透性超氧化物歧化酶模拟物 Mn(III) 四苯甲酸卟啉 (MnTBAP) 的共同处理来预防。我们的结果表明，心肌细胞凋亡可能不需要从头合成蛋白质，而蛋白质合成抑制本身就会导致心肌细胞凋亡。（2）在培养的新生大鼠离体肌细胞中，缺氧和葡萄糖剥夺（体外缺血）导致收缩间隔增加和搏动波动。节奏。然而，在体外缺血期间，肌细胞之间的同步保持不变。这一结果表明，在缺氧/缺血期间，肌细胞之间的间隙连接可能保持开放。(3)在成年大鼠的Langendorff灌注心脏中，整体缺血导致心脏周期延长，心脏最终在约10分钟内停止跳动。然而，在大多数 Langendorff 制剂中，再灌注后心跳节律恢复到控制状态。在某些情况下，再灌注会引起心律失常样不规则搏动。