ARGININE-VASOPRESSIN V-1-RECEPTOR ANTAGONISM IN AN OVINE MODEL OF ACUTE MYOCARDIAL-INFARCTION

Arginine vasopressin (AVP) has an uncertain role in the pathogenesis o f increased myocardial and other regional vascular resistance after ca rdiac injury. The extreme increase in plasma AVP levels observed in so me individuals after myocardial infarction potentially exacerbates alr eady compromised myocardial perfusion. We assessed whether blockade of AVP, by administration of the specific V-1-receptor antagonist OPC-21 268, can reduce the severity of myocardial injury after embolization i n our ovine model of acute myocardial infarction. Embolizations result ed in a pattern of changes in ECG and cardiac enzymes consistent with moderate to severe acute myocardial infarction, resulting in left vent ricular dysfunction [left ventricular ejection fraction (LVEF) reduced from 52-53% to 38%]. However, no statistically significant difference s were observed between groups in hemodynamic or neurohumoral indices of myocardial damage. By contrast, the hypothalamus-pituitary-adrenal (HPA) response [including plasma AVP (p < 0.01), adrenocorticotropic h ormone (ACTH; p < 0.01), and cortisol (p < 0.01)) to embolizations was significantly increased in the sheep infused with OPC-21268. In concl usion, whereas plasma HPA responses differed between the two groups, t he similar responses in cardiac enzymes, LVEF, and hemody namic and ne urohumoral factors in both groups does not support a role of V-1 recep tor-mediated exacerbation of myocardial injury in this model of myocar dial infarction. Assessment of different receptor antagonists or exami nation of other models of cardiac injury may further clarify the role of the markedly increased AVP levels that can occur in myocardial infa rction.