Effects of acrihellin, a new cardiosteroid, compared to digoxin, MDL 17043, and milrinone in the pentobarbital-compromised dog

Autor: Cindy De Vine, Leo B. Czyzewski, Mary Asaad, William Diamantis, R. Duane Sofia
Rok vydání: 1991
Předmět:
Zdroj: Drug Development Research. 24:189-199
ISSN: 1098-2299
0272-4391
DOI: 10.1002/ddr.430240206
Popis: Acrihellin, digoxin, MDL 17043, and milrinone were administered intravenously in the anesthetized dog to compare their effects on the cardiovascular parameters following pentobarbital-induced heart failure. Dogs were instrumented to record left ventricular pressure, the derivative of the left ventricular pressure (dP/dt max), mean arterial pressure, heart rate, cardiac output, stroke volume, and total peripheral resistance. Pentobarbital compromise caused significant decreases from baseline in all cardiovascular parameters and slightto-marked increases in stroke volume and left ventricular end-diastolic pressure. Following pentobarbital-induced heart failure, acrihellin reversed the cardiovascular changes with dose-dependent, positive inotropic effects (dP/dt max), decreases in left ventricular enddiastolic pressure, and increases in stroke volume and cardiac output. Acrihellin caused a significant shift upwards and to the left of the stroke volume index/left ventricular enddiastolic slope at peak inotropy (45 min). Comparable, but nonsignificant, shifts were evident with each of the three standard compounds at peak inotropy: digoxin at 45 min, MDL 17043 at 5 min, and milrinone at 5 min. The intravenous drug doses were 45 μg/kg (1 molar equivalent) for acrihellin, 70.5 μg/kg (1 molar equivalent) for digoxin, 59.75 μg/kg (3 molar equivalents) for MDL 17043, and 38.1 μg/kg (2 molar equivalents) for milrinone. The present findings indicate that acrihellin is a potent cardiotonic drug as demonstrated in the failing heart dog model following pentobarbital.
Databáze: OpenAIRE
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