Hemodynamic profile of the new cardiotonic agent CK‐2289 compared to milrinone and enoximone in the anesthetized dog

Abstract

AbstractWe examined the hemodynamic profile of CK‐2289, a new imidazolone developed for the treatment of congestive heart failure, in the normal pentobarbital‐anesthetized dog. Mongrel dogs (10–18 kg) of either sex were anesthetized with pentobarbital sodium (35 mg/kg, intravenously [i.v.]) and instrumented for routine hemodynamic measurements using an open‐chest, artificially ventilated preparation. Intravenous administration of CK‐2289 (3, 10, 30, and 100 μ/kg) to pentobarbital‐anesthetized dogs increased left ventricular (LV) dP/dTmax by 9, 26, 73, and 80%, respectively, and decreased mean arterial pressure (MAP) by 2, 6, 18, and 34%. CK‐2289 was 2.7 times more potent as a positive inotropic agent than as a vasodilator. Heart rate (HR) increased by 2, 10, 18, and 28% after these doses of CK‐2289, while left ventricular end diastolic pressure (LVEDP) decreased by 4.5 mmHg after the highest dose of compound. CK‐2289 increased coronary blood flow (CBF) after each dose of compound. However, the increased CBF was less than that produced by milrinone for equivalent increases in LV dP/dTmax. Renal blood flow increased while vertebral blood flow was reduced after administration of the two highest doses of CK‐2289. However, vertebral vascular resistance decreased slightly from control values. Milrinone and enoximone behaved qualitatively similar to, but were 6 and 27 times less potent than CK‐2289 as cardiotonic agents. Thus, CK‐2289 is a mixed positive inotrope and vasodilator with a hemodynamic profile similar to milrinone and enoximone, which sugests it may have utility in the treatment of heart failure.