Chagoya de Sánchez V, Hernández-Muñoz R, López-Barrera F, Yañez L, Vidrio S, Suárez J, Cota-Garza M D, Aranda-Fraustro A, Cruz D
Departamento de Bioenergética, Instituto de Fisiología Celular, UNAM, México.
Can J Physiol Pharmacol. 1997 Dec;75(12):1300-11.
Acute myocardial infarction is the second cause of mortality in most countries, therefore, it is important to know the evolution and sequence of the physiological and biochemical changes involved in this pathology. This study attempts to integrate these changes and to correlate them in a long-term model (96 h) of isoproterenol-induced myocardial cell damage in the rat. We achieved an infarct-like damage in the apex region of the left ventricle, occurring 12-24 h after isoproterenol administration. The lesion was defined by histological criteria, continuous telemetric ECG recordings, and the increase in serum marker enzymes, specific for myocardial damage. A distinction is made among preinfarction, infarction, and postinfarction. Three minutes after drug administration, there was a 60% increase in heart rate and a lowering of blood pressure, resulting possibly in a functional ischemia. Ultrastructural changes and mitochondrial swelling were evident from the first hour of treatment, but functional alterations in isolated mitochondria, such as decreases in oxygen consumption, respiratory quotient, ATP synthesis, and membrane potential, were noticed only 6 h after drug administration and lasted until 72 h later. Mitochondrial proteins decreased after 3 h of treatment, reaching almost a 50% diminution, which was maintained during the whole study. An energy imbalance, reflected by a decrease in energy charge and in the creatine phosphate/creatine ratio, was observed after 30 min of treatment; however, ATP and total adenine nucleotides diminished clearly only after 3 h of treatment. All these alterations reached a maximum at the onset of infarction and were accompanied by damage to the myocardial function, drastically decreasing left ventricular pressure and shortening the atrioventricular interval. During postinfarction, a partial recovery of energy charge, creatine phosphate/creatine ratio, membrane potential, and myocardial function occurred, but not of mitochondrial oxygen consumption, rate of ATP synthesis, total adenine nucleotides, or mitochondrial proteins. Interesting correlations of the sequential changes in heart and mitochondrial functions with energy metabolism were obtained at different stages of the isoproterenol-induced cardiotoxicity. These correlations could be useful to study and understand the cellular events involved in this pathology.
急性心肌梗死是大多数国家第二大死因，因此，了解该病理过程中生理和生化变化的演变及顺序很重要。本研究试图整合这些变化，并将其与异丙肾上腺素诱导的大鼠心肌细胞损伤长期模型（96小时）相关联。我们在左心室心尖区域实现了类似梗死的损伤，在给予异丙肾上腺素后12 - 24小时出现。通过组织学标准、连续遥测心电图记录以及心肌损伤特异性血清标志物酶的升高来定义该病变。区分了梗死前期、梗死期和梗死后期。给药三分钟后，心率增加60%，血压降低，可能导致功能性缺血。从治疗的第一个小时起，超微结构变化和线粒体肿胀就很明显，但仅在给药6小时后才注意到分离线粒体的功能改变，如氧消耗、呼吸商、ATP合成和膜电位降低，并持续到72小时后。治疗3小时后线粒体蛋白减少，几乎减少了50%，在整个研究过程中一直保持。治疗30分钟后观察到能量失衡，表现为能量电荷以及磷酸肌酸/肌酸比值降低；然而，ATP和总腺嘌呤核苷酸仅在治疗3小时后才明显减少。所有这些改变在梗死开始时达到最大值，并伴有心肌功能损伤，左心室压力急剧下降，房室间期缩短。在梗死后期，能量电荷、磷酸肌酸/肌酸比值、膜电位和心肌功能部分恢复，但线粒体氧消耗、ATP合成速率、总腺嘌呤核苷酸或线粒体蛋白未恢复。在异丙肾上腺素诱导的心脏毒性不同阶段，获得了心脏和线粒体功能的顺序变化与能量代谢的有趣相关性。这些相关性可能有助于研究和理解该病理过程中涉及的细胞事件。
