title: Effect of dobutamine and OPC-18790 on diastolic chamber stiffness in patients with idiopathic dilated cardiomyopathy.
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 micrograms/kg body weight per min, n = 8) or OPC-18790 (5-10 micrograms/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 < 0.01) and OPC-18790 (0.0843 +/- 0.0477 to 0.0569 +/- 0.0246; p < 0.05) groups. The passive diastolic chamber stiffness constant decreased significantly in the OPC-18790-treated group (0.0211 +/- 0.0114 to 0.0144 +/- 0.0117; p < 0.005) but not in the dobutamine-treated group (0.0197 +/- 0.0130 to 0.010186 +/- 0.0102; 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.
authors.affiliation: First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Machii
authors.forename: M
authors.initials: M
authors.lastname: Yokota
authors.forename: K
authors.initials: K
authors.lastname: Nagata
authors.forename: H
authors.initials: H
authors.lastname: Ishihara
authors.forename: M
authors.initials: M
authors.lastname: Iwase
authors.forename: T
authors.initials: T
authors.lastname: Sobue
mesh_terms: D000328:Adult; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003971:Diastole / Q000187:drug effects*; D004280:Dobutamine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D015363:Quinolones; C077543:toborinone; D004280:Dobutamine