title: Sequential changes of energy metabolism and mitochondrial function in myocardial infarction induced by isoproterenol in rats: a long-term and integrative study.
abstract: 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.
authors.affiliation: Departamento de Bioenergética, Instituto de Fisiología Celular, UNAM, México.
authors.forename: V
authors.initials: V
authors.lastname: Chagoya de Sánchez
authors.forename: R
authors.initials: R
authors.lastname: Hernández-Muñoz
authors.forename: F
authors.initials: F
authors.lastname: López-Barrera
authors.forename: L
authors.initials: L
authors.lastname: Yañez
authors.forename: S
authors.initials: S
authors.lastname: Vidrio
authors.forename: J
authors.initials: J
authors.lastname: Suárez
authors.forename: M D
authors.initials: MD
authors.lastname: Cota-Garza
authors.forename: A
authors.initials: A
authors.lastname: Aranda-Fraustro
authors.forename: D
authors.initials: D
authors.lastname: Cruz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents; D004487:Edema / Q000150:complications / Q000473:pathology; D004594:Electrophysiology; D004734:Energy Metabolism / Q000187:drug effects*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol; D008297:Male; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; D007545:Isoproterenol