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(Circulation. 1996;93:474-483.)
© 1996 American Heart Association, Inc.

Articles

Acute Cardiovascular Effects of OPC-18790 in Patients With Congestive Heart Failure

Time- and Dose-Dependence Analysis Based on Pressure-Volume Relations

Marc D. Feldman, MD; Peter H. Pak, MD; Clarence C. Wu, MS; Howard L. Haber, MD; Christian M. Heesch, MD; James D. Bergin, MD; Eric R. Powers, MD; T. Douglas Cowart, PhD; William Johnson, RN; Arthur M. Feldman, MD, PhD; David A. Kass, MD

From the Divisions of Cardiology and the Departments of Internal Medicine, the Johns Hopkins Medical Institutions, Baltimore, Md, and the University of Virginia Health Sciences Center, Charlottesville.

Correspondence to David A. Kass, MD, Division of Cardiology, Halsted 500, Johns Hopkins University Hospital, 600 N Wolfe St, Baltimore, MD 21287.

Background OPC-18790 is a water-soluble quinolinone derivative that shares the pharmacological properties of vesnarinone and that may be useful for treating heart failure. We studied the contribution and relative dose sensitivities of the inotropic, lusitropic, and vascular effects of OPC-18790 in patients with dilated cardiomyopathy.

Methods and Results Pressure-volume (PV) analysis was performed in 17 patients who received either 5 µg·kg^-1·min^-1 (low dose, n=10) or 10 µg·kg^-1·min^-1 (high dose, n=7) OPC-18790 by 1-hour IV infusion. Right heart pressures and flow and left heart PV relations (conductance catheter) were measured at baseline and every 15 minutes during infusion. Transient inferior vena caval obstruction was used to determine PV relations. Both doses produced venodilation reflected by a 10% decline in left ventricular end-diastolic volume and a 30% fall in atrial and pulmonary artery pressures. Arterial dilation was four times greater at the high dose, with an 40% fall in effective arterial elastance and systemic resistance. Contractility rose by 25% to 100% (depending on PV index) with both doses. Ventricular-arterial coupling (ratio of ventricular end-systolic to arterial elastances) was 0.25 at baseline and doubled (or tripled) at low (or high) dose, correlating with improved efficiency. Isovolumetric relaxation shortened, whereas the diastolic PV relation was generally unchanged. Heart rate was unaltered.

Conclusions OPC-18790 has potent venous and arterial vasodilator effects and moderate inotropic and lusitropic effects without a change in heart rate. These combined actions suggest a unique potential of OPC-18790 for heart failure treatment.

Key Words: cardiomyopathy • inotropic agents • heart failure • hemodynamics • quinolinone

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