Role of Nitric Oxide in Isoproterenol-Induced Myocardial Infarction

Abstract

Myocardial infarction (MI) is an important cause of mortality around the world, resulting from an ischemic necrosis induced by a vascular occlusion. In general, MI occurs unexpectedly and the clinical syndrome previous to MI is difficult to detect. Animal models of MI are very useful in the study of prevention, diagnosis and therapy design for human MI [Srnith & Nuttall., 19851.MI induced by ligation of the left anterior descending coronary artery is the animal model most frequently used; however, the anesthesia and surgical procedures affect the conditions in which the infarction occurred [Wang et al., 20061. Therefore, MI in animal models studies should be induced in conscious animals with intact reflexes for greater clinical relevance. Myocardial infarction induced by isoproterenol (ICO) using toxic concentration of this P-adrenergic agonist drug, originally described by Rona [Rona et al., 19591 has been used by severa1 groups to study the cardiotoxic effects of this molecule [Stanton et a1,1969]. This model becomes relevant if we consider that increased adrenergic activation plays a role as a trigger of acute myocardial infarction. In addition, the stress associated to MI in patients, increases catecholamine blood levels, which in turn, augment contraction force of the heart and.ATP utilization favoring an energetic unbalance [Wallace & Klein, 1969, Ueba et al, 19731. We have used ICO-induced MI, which is a non-invasive experimental model, to study the mechanisms involved in MI in the steps previous and posterior to infarction [Chagoya de Sánchez et al., 1997. Myocardial lesions induced by ICO are related to its cardiac stimulating properties [Chappel et a1.,1959]. Our group has characterized histological, physiological and biochemical alterations in a long term model (0-96h) of ICO administration to rats [Chagoya de Sánchez et al., 1997. Animals treated with ISO showed an infarct-like damage of the circumferential type in the subendocardium at the apex region of the left ventricle that