Hibernating myocardium - Chronically adapted to ischemia but vulnerable to sudden death
Hibernating myocardium - Chronically adapted to ischemia but vulnerable to sudden death
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DOI：
10.1161/01.res.0000125628.57672.cf
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发表时间：
2004-04-30
影响因子：
20.1
通讯作者：
Fallavollita, JA
中科院分区：
文献类型：
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作者：
Canty, JM;Suzuki, G;Fallavollita, JA
在慢性冠状动脉疾病的动物模型中不能再现自发性心室颤动限制了对心源性猝死（SCD）机制的理解。由慢性左前降支冠状动脉（LAD）闭塞引起的冬眠心肌猪的SCD发生率较高，这与冬眠心肌经药物治疗患者的临床生存率较差平行。Kaplan-Meier分析（n=426）显示，5个月后的累积死亡率为49%，几乎完全归因于自发性SCD。使用植入式回路记录器，将室颤记录为所有动物（n=10）的死亡病理机制，并且通常在室性心动过速（n=8）之前发生。SCD前的生理学研究（n=7）证实LAD完全闭塞和侧支依赖性心肌（n=5），排除急性闭塞作为心律失常的主要触发因素。SCD前存在冬眠心肌的生理基质，LAD灌注减少（SCD 0.79+/-0.13 vs 0.80+/-0.08 mL/min/g）和壁增厚（SCD 28+/-3% vs 22+/-3%），与存活者相似（n=14）。SCD动物中氯化三苯基四氮唑梗死罕见（32只中的4只）且较小，平均为LV质量的4.6%。组织学（n=4）显示死后变化，但无急性炎症或收缩带坏死。这些数据支持冬眠心肌是SCD高风险的病理生理学底物的观点。这与功能性狭窄严重程度、急性心肌坏死或纤维化瘢痕的变化无关。因此，在慢性重复性缺血的情况下促进肌细胞存活的区域适应导致对致命性心律失常和SCD具有增强的脆弱性的基质。
The inability to reproduce spontaneous ventricular fibrillation in an animal model of chronic coronary artery disease has limited advances in understanding mechanisms of sudden cardiac death (SCD). Swine with hibernating myocardium arising from a chronic left anterior descending coronary artery (LAD) occlusion have a high rate of SCD that parallels the poor clinical survival of medically treated patients with hibernating myocardium. Kaplan-Meier analysis (n=426) demonstrated a cumulative mortality of 49% after 5 months that was almost entirely attributable to spontaneous SCD. Using implantable loop recorders, ventricular fibrillation was documented as the arrhythmic mechanism of death in all animals (n=10) and was usually preceded by ventricular tachycardia (n=8). Physiological studies before SCD (n=7) demonstrated total LAD occlusion and collateral-dependent myocardium (n=5), excluding acute occlusion as a major trigger of arrhythmia. The physiological substrate of hibernating myocardium was present before SCD, with reductions in LAD perfusion (SCD 0.79+/-0.13 versus 0.80+/-0.08 mL/min per g) and wall thickening (SCD 28+/-3% versus 22+/-3%) that were similar to survivors (n=14). Triphenyltetrazolium chloride infarcts among animals with SCD were infrequent (4 of 32) and small, averaging 4.6% of LV mass. Histology (n=4) showed postmortem changes but no acute inflammation nor contraction band necrosis. These data support the notion that hibernating myocardium is a pathophysiological substrate at high risk of SCD. This is independent of changes in functional stenosis severity, acute myocardial necrosis, or fibrotic scar. Thus, regional adaptations that promote myocyte survival in the setting of chronic repetitive ischemia result in a substrate with enhanced vulnerability to lethal arrhythmias and SCD.