Document Detail


Cardiac and hemodynamic profile of the new cardiotonic agent, DPI 201-106, in the conscious dog.
MedLine Citation:
PMID:  2767134     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cardiac and hemodynamic effects of increasing doses (0.1-3 mg/kg i.v.) of the novel cardiotonic agent, DPI 201-106 (DPI), were investigated over a 60 min period in conscious dogs chronically instrumented for the measurement of arterial pressure, heart rate, left ventricular pressure (LVP), LV (+) dP/dtmax and cardiac output. LV (+) dP/dtmax, cardiac output and stroke volume were significantly increased by DPI whereas the total peripheral resistance was significantly decreased. These effects were dose-dependent in intensity and in duration. The mean arterial pressure and heart rate remained unaffected, except by the 3 mg/kg dose, which increased them slightly. Autonomic blockade with hexamethonium, atropine and propranolol did not alter the positive inotropic properties of DPI but unmasked its intrinsic bradycardic effect. At equipotent positive inotropic doses, DPI (0.3 mg/kg), milrinone (40 micrograms/kg) and dobutamine (5 micrograms/kg per min) induced similar increases in cardiac output and similar decreases in total peripheral resistance, but only dobutamine and milrinone accelerated the heart rate, whereas ouabain (17.5 micrograms/kg) induced a strong rise in the total peripheral resistance and markedly lowered the heart rate and cardiac output. After coadministration of DPI and ouabain, LV (+) dP/dtmax was further increased whereas the ouabain-induced bradycardia, the rise in the total peripheral resistance and the decrease in cardiac output were reinforced, halved and unaltered, respectively. We conclude that (a) DPI exhibits potent and direct positive inotropic properties, associated with a peripheral vasodilating action, and almost no positive chronotropic effects, and (b) coadministration of DPI and ouabain results in synergistic positive inotropic effects.
Authors:
J L Gerard; A Berdeaux; J F Giudicelli
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  165     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1989 Jun 
Date Detail:
Created Date:  1989-10-05     Completed Date:  1989-10-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  39-49     Citation Subset:  IM    
Affiliation:
Département de Pharmacologie, Faculté de Médecine Paris-Sud, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Autonomic Nervous System / drug effects
Cardiotonic Agents*
Dobutamine / pharmacology
Dogs
Drug Interactions
Female
Heart / drug effects*
Hemodynamics / drug effects*
Male
Milrinone
Myocardial Contraction / drug effects
Ouabain / pharmacology
Piperazines / pharmacology*
Pyridones / pharmacology
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Piperazines; 0/Pyridones; 34368-04-2/Dobutamine; 630-60-4/Ouabain; 78415-72-2/Milrinone; 97730-95-5/DPI 201-106

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


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