Document Detail


Acute cardiovascular effects of OPC-18790 in patients with congestive heart failure. Time- and dose-dependence analysis based on pressure-volume relations.
MedLine Citation:
PMID:  8565164     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 micrograms.kg-1.min-1 (low dose, n = 10) or 10 micrograms.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 approximately 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 approximately 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.
Authors:
M D Feldman; P H Pak; C C Wu; H L Haber; C M Heesch; J D Bergin; E R Powers; T D Cowart; W Johnson; A M Feldman; D A Kass
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  93     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-03-04     Completed Date:  1996-03-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  474-83     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, Md, USA.
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MeSH Terms
Descriptor/Qualifier:
Blood Pressure*
Cardiomyopathy, Dilated / drug therapy,  physiopathology*
Cardiotonic Agents / administration & dosage,  pharmacology*,  therapeutic use
Heart Rate / drug effects
Humans
Quinolones / administration & dosage,  pharmacology*,  therapeutic use
Stroke Volume*
Grant Support
ID/Acronym/Agency:
AG-12249/AG/NIA NIH HHS; HL-47046/HL/NHLBI NIH HHS; HL-47511/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Quinolones; 128667-95-8/torborinone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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