Systemic and regional hemodynamic effects of isomazole in awake dogs with congestive heart failure.

Abstract

To determine the hemodynamic effects of isomazole, an imidazopyridine, we administered isomazole (10 and 20 micrograms/kg/min) to 10 awake dogs with right-sided congestive heart failure produced by pulmonary artery constriction and tricuspid valve avulsion. Isomazole increased cardiac output, heart rate, right ventricular and left ventricular (LV) dP/dt, LVdP/dt/P and decreased aortic pressure and total peripheral vascular resistance. Simultaneously, blood flow increased to myocardium, quadriceps muscle, brain and splanchnic beds, whereas vascular resistance decreased. Furthermore, isomazole increased LV oxygen consumption and decreased transcoronary arteriovenous oxygen difference. Similar administration of normal saline had no effects. Angiotensin II was infused to restore mean aortic pressure to base-line values during isomazole infusion; however, despite the return of aortic pressure to base-line values, cardiac output, LVdP/dt and LVdP/dt/P remained elevated. The systemic and regional hemodynamic effects of isomazole were unaffected by pretreatment with propranolol and mecamylamine. Thus, isomazole exerted positive inotropic, chronotropic and vasodilator effects in congestive heart failure dogs. The inotropic effect of isomazole was independent of the decrease in aortic pressure, and the hemodynamic effects of isomazole were not mediated via the autonomic nervous system. Furthermore, the decrease in transcoronary arteriovenous oxygen difference suggests that isomazole exerted an active coronary vasodilator action which may improve myocardial oxygen demand/supply ratio.

• Authors: N Imai, C S Liang, C K Stone, J S Hayes, W B Hood Jr
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 241 Issue 1 Pg. 20-6 (Apr 1987) ISSN: 0022-3565 [Print] United States
• PMID: 3572783 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Catecholamines
• Imidazoles
• Angiotensin II
• Propranolol
• sulmazole
• Isoproterenol

Topics

• Angiotensin II (pharmacology)
• Animals
• Cardiac Output (drug effects)
• Catecholamines (blood)
• Dogs
• Heart Failure (drug therapy)
• Heart Rate (drug effects)
• Hemodynamics (drug effects)
• Imidazoles (therapeutic use)
• Isoproterenol (pharmacology)
• Myocardial Contraction (drug effects)
• Propranolol (pharmacology)
• Regional Blood Flow (drug effects)
• Sympathetic Nervous System (drug effects)
• Vascular Resistance (drug effects)
• Vasodilation (drug effects)