Echocardiographic and clinical effects of milrinone in dogs with myocardial failure

Abstract

SUMMARY Milrinone is a recently synthesized bypyridine compound with positive inotropic and arteriolar dilating properties in persons and experimental animals. To examine the efficacy and safety of milrinone to treat myocardial failure in dogs, dogs with myocardial failure were selected from the patient populations of 3 veterinary hospitals. Progressively increased dosages of milrinone, from 0.05 to 1.0 mg/kg of body weight, were administered over 14 days, and cardiac responses, as determined by M-mode echocardiography, and clinical responses were recorded. An effective dosage of milrinone was identified for each dog and administered for 4 weeks to evaluate the stability of the cardiac response. A randomized blinded study of drug vs nondrug capsule or nondrug elixer (designated placebo) was performed at the end of 4 weeks to eliminate possible effects of investigator bias or spontaneous regression of the disease. The duration of drug effect was determined by evaluating echocardiographic measurements of left ventricular function for 12 hours after drug administration. Echocardiographic evaluation of left ventricular function improved in dogs given milrinone. The effective dosage was between 0.5 and 1.0 mg/kg. Tolerance to milrinone did not develop during the 4-week study. In dogs given placebo during the randomized blinded study, echocardiographic values decreased significantly. Dogs that were given milrinone remained echocardiographically stable. During the study, 6 dogs improved clinically, 5 remained the same, 1 had a decrease in exercise tolerance, 1 died of severe heart failure, and 1 died of hypoadrenocorticism. Ventricular tachydysrhythmia was exacerbated in 2 dogs, but was not treated. The drug effect lasted 12 hours, but was only 45% of maximum at 12 hours. This study indicates that milrinone may be, in the future, an effective and safe drug for treating myocardial failure in the dog.