Acute effects of milrinone on the electrocardiogram and the cardiac hemodynamics of rats with pressure overload-induced congestive heart failure.
The effects of i.v. bolus injections of milrinone on the electrocardiogram and cardiac hemodynamics were evaluated in old rats with chronic (82-93 weeks) pressure overload induced by aortic constriction. Based on the heart weight/body weight ratio and histopathological findings, the rats with aortic clips were divided into 2 groups: rats with (CHF group) or without (CLIP group) congestive heart failure (CHF). In CHF rats, the cardiac contractility, as measured by the peak of the first derivative of the left ventricular pressure (dP/dt max), was significantly lower than in CLIP rats, confirming the presence of heart failure in these rats. Three groups of anesthetized rats received boluses of milrinone of 0.1, 0.5, 1, 5 and 10 mg/kg: sham-operated rats (SHAM, n = 9), CLIP (n = 22) and CHF (n = 10). A control group of 3 CHF and 5 CLIP rats received only the vehicle. The major effect of milrinone at the 2 highest doses was the induction of ventricular fibrillation and death in approximately 25% of the rats (SHAM 2/9, CHF 1/10 and CLIP 7/22). A significant widening of the QRS complex (which includes ST segment) was also noted 3 min after each dose of milrinone in the SHAM group and at 5 and 10 mg/kg doses in the CHF group. These results were thought to be related to the marked hypotensive effect of milrinone possibly inducing myocardial ischemia. No positive inotropic effect, as indicated by the maximum rise of left ventricular pressure (dP/dt max) could be observed. This might have been because of (1) the marked vasodilating effect of milrinone on venous and arterial beds, negating a possible small positive inotropic effect, or (2) the lack of positive inotropic action of milrinone in rats. Our results thus indicate that, in anesthetized rats, milrinone is a powerful vasodilator but not a positive inotropic agent (or a very weak one).
Desjardins
S
S
Health Protection Branch, Bureau of Drug Research, Tunney's Pasture, Ottawa, Ontario, Canada.
Cauchy
M J
MJ
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004562:Electrocardiography; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D020105:Milrinone; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002316:Cardiotonic Agents; D011728:Pyridones; D020105:Milrinone