Arginine vasopressin V1-receptor antagonism in an ovine model of acute myocardial infarction.
Arginine vasopressin (AVP) has an uncertain role in the pathogenesis of increased myocardial and other regional vascular resistance after cardiac injury. The extreme increase in plasma AVP levels observed in some individuals after myocardial infarction potentially exacerbates already compromised myocardial perfusion. We assessed whether blockade of AVP, by administration of the specific V1-receptor antagonist OPC-21268, can reduce the severity of myocardial injury after embolization in our ovine model of acute myocardial infarction. Embolizations resulted in a pattern of changes in ECG and cardiac enzymes consistent with moderate to severe acute myocardial infarction, resulting in left ventricular dysfunction [left ventricular ejection fraction (LVEF) reduced from 52-53% to 38%]. However, no statistically significant differences 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 hormone (ACTH; p < 0.01), and cortisol (p < 0.01)) to embolizations was significantly increased in the sheep infused with OPC-21268. In conclusion, whereas plasma HPA responses differed between the two groups, the similar responses in cardiac enzymes, LVEF, and hemodynamic and neurohumoral factors in both groups does not support a role of V1 receptor-mediated exacerbation of myocardial injury in this model of myocardial infarction. Assessment of different receptor antagonists or examination of other models of cardiac injury may further clarify the role of the markedly increased AVP levels that can occur in myocardial infarction.
Charles
C J
CJ
Department of Medicine, Christchurch School of Medicine, New Zealand.
Donald
R A
RA
Ikram
H
H
Prickett
T
T
Richards
A M
AM
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D005260:Female; D006221:Halothane / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D010880:Piperidines / Q000627:therapeutic use*; D015363:Quinolones / Q000627:therapeutic use*; D012083:Renin / Q000097:blood; D012756:Sheep
D065092:Antidiuretic Hormone Receptor Antagonists; D010880:Piperidines; D015363:Quinolones; D001127:Arginine Vasopressin; C068644:OPC 21268; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D012083:Renin; D006221:Halothane