Comparative cardiac effects of milrinone and sodium nitroprusside in conscious rats.
The rat has been shown to be resistant to the inotropic action of milrinone. We compared in conscious rats, the effects of an i.v. infusion of milrinone (0.3 mg/kg/min), a phosphodiesterase (PDE) inhibitor to those of nitroprusside (50 micrograms/kg/min), a pure vasodilator, on blood pressure and dP/dtmax to determine whether or not an inherent positive inotropic effect of milrinone is offset by its powerful hypotensive action. For the first 10 min of infusion, we found no differences in dP/dtmax, (the first derivative of the left ventricular pressure (LVP), an index of contractility) for equihypotensive doses of milrinone or nitroprusside. A second objective of this study was to determine if milrinone-induced ventricular fibrillation (VF) is due to cardiac ischemia which could be associated with the profound hypotension induced by the drug. Milrinone infusion was accompanied by a significant QTc interval (QT corrected for heart rate) prolongation. VF and death occurred in 5/6 rats at total doses varying from 3.6 to 20.1 mg/kg infused over 12 to 67 min respectively. Premature ventricular contractions (PVCs) were noted in all 6 milrinone infused rats during the first min. of infusion. No arrhythmias were noted during the 2 hour i.v. infusion with nitroprusside. A direct action on the heart is postulated to explain, at least partially, the milrinone-induced VF since nitroprusside had a similar hypotensive action but no effect on the ECG. We conclude that the rat, in analogy to patients with severe cardiac failure, might be resistant to the inotropic action of milrinone but is sensitive to its vasodilatory and arrhythmogenic effects.
Desjardins
S
S
Biopharmaceutics and Pharmacodynamics Division, Bureau of Drug Research, Health Protection Branch, Ottawa, Ontario, Canada.
Cauchy
M J
MJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology* / Q000633:toxicity; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000633:toxicity; D011728:Pyridones / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000633:toxicity; D014693:Ventricular Fibrillation / Q000139:chemically induced*
D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D014665:Vasodilator Agents; D009599:Nitroprusside; D020105:Milrinone