Document Detail


Effects of OPC-18790, a new positive inotropic agent, on energetics in the ischaemic canine heart: a 31P-MRS study.
MedLine Citation:
PMID:  7585818     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Effects of OPC-18790, a novel positive inotropic agent, on cardiohaemodynamics and cardiac energetics were assessed simultaneously in dogs with cardiac ischaemia using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) and compared with those of amrinone, a pure cGMP-inhibited PDE inhibitor. METHODS: Cardiac ischaemia was produced by partial stenosis of the coronary artery. Dogs with cardiac ischaemia were instrumented for the determination of regional coronary blood flow (non-radioactive coloured microsphere method), regional contractile function (sonomicrometry), and haemodynamics. Myocardial phosphate compounds were measured simultaneously by 31P-MRS. RESULTS: Coronary stenosis produced regional dyskinesis, a slight decrease in cardiac output (CO), intracellular acidosis, an increase in the inorganic phosphate (Pi)/creatine phosphate (PCr) ratio concomitantly with a decrease in regional coronary blood flow (CBF) in the ischaemic region. OPC-18790 dose-dependently produced an increase in contractility (measured by peak LVdP/dt) and CO, with only slight changes in heart rate (HR) and mean blood pressure (mBP). OPC-18790 did not change regional dyskinesis, but improved the Pi/PCr ratio at the high dose compared with ischaemic values (before drug administration). Amrinone produced an increase in CO comparable to that of OPC-18790; however, the increase in peak LVdP/dt was smaller while the increase in HR and decrease in mBP were larger than those seen with OPC-18790. Amrinone worsened the Pi/PCr ratio and intracellular acidosis only at the high dose. CONCLUSION: These observed differences in energy metabolism between OPC-18790 and amrinone at the high dose may be due to the ability of OPC-18790 to increase CBF in the ischaemic region and which may attributed to its differing effect on overall haemodynamics. Thus, OPC-18790 may be useful in the management of ischaemic heart failure.
Authors:
M Ishikawa; T Mori; S Itoh; H Fujiki; K Koga; M Tominaga; Y Yabuuchi
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Cardiovascular research     Volume:  30     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-12-12     Completed Date:  1995-12-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  299-306     Citation Subset:  IM    
Affiliation:
2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amrinone / pharmacology
Animals
Blood Pressure / drug effects
Cardiotonic Agents / pharmacology*
Coronary Circulation / drug effects
Dogs
Dose-Response Relationship, Drug
Energy Metabolism / drug effects*
Female
Heart Rate / drug effects
Magnetic Resonance Imaging
Male
Myocardial Contraction / drug effects*
Myocardial Ischemia / metabolism*
Myocardium / metabolism
Quinolones / pharmacology*
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Quinolones; 128667-95-8/torborinone; 60719-84-8/Amrinone

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


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