Effect of Dobutamine and OPC-18790 on Diastolic Chamber Stiffness in Patients with Idiopathic Dilated Cardiomyopathy

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Abstract
We investigated the acute effects of the positive inotropic agents (dobutamine and a novel phosphodiesterase inhibitor OPC-18790) on left ventricular diastolic chamber stiffness in patients with idiopathic dilated cardiomyopathy (DCM). We obtained pressure-volume (PV) data before and after drug administration in 17 patients with DCM by using a conductance catheter with a micromanometer tip. Patients were randomly assigned to receive intravenous infusions of dobutamine (2.5-7.5 μg/kg body weight per min, n = 8) or OPC-18790 (5-10 μg/kg body weight per min, n = 9). The dynamic diastolic chamber stiffness constant was calculated from a steady-state beat. The passive diastolic chamber stiffness constant was determined from the end-diastolic PV relation determined during transient inferior vena caval occlusion. Dobutamine and OPC-18790 similarly improved left ventricular end-systolic elastance (Ees) and left ventricular isovolumic relaxation time constants. The dynamic diastolic chamber stiffness constant decreased significantly in both the dobutamine (0.0934 ± 0.0271 to 0.0685 ± 0.0248; p 0.05). Thus both dobutamine and OPC-18790 reduced the dynamic diastolic chamber stiffness constant, but only OPC-18790 reduced the passive diastolic chamber stiffness constant. OPC-18790 had a favorable effect on diastolic function in patients with DCM, compared with that of dobutamine. The passive diastolic chamber stiffness obtained from the end-diastolic PV relations represents more likely passive chamber properties than the dynamic diastolic chamber stiffness obtained from traditional single-beat analysis.