Document Detail


The cardiac effects of pimobendan (but not amrinone) are preserved at rest and during exercise in conscious dogs with pacing-induced heart failure.
MedLine Citation:
PMID:  9223536     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We compared the effects of pimobendan (0.25 mg/kg i.v.), a Ca++ sensitizer, with some phosphodiesterase-III inhibition effects, and amrinone (1 mg/kg plus 10 microg/kg/min i.v.), a PDE-III inhibitor, on left ventricular (LV) systolic and diastolic performance, both at rest and during exercise, in seven conscious dogs before and after pacing-induced congestive heart failure (CHF). Before CHF, under resting conditions, both pimobendan and amrinone caused a similar significant decrease in left ventricle size and end-systolic pressure, arterial elastance, and the time constant of LV relaxation. Similar results were obtained during exercise. Both agents also produced a similar increase in E(ES), the slope of the LV end-systolic pressure-volume relation (3.4 +/- 1.5 vs. 4.2 +/- 1.1 mm Hg/ml; amrinone vs. pimobendan). After CHF, the vasodilatory effects of amrinone and pimobendan were preserved both at rest and during exercise; however, the inotropic actions were different. After CHF, pimobendan increased E(ES) (3.9 +/- 0.5 vs. 5.7 +/- 0.4 mm Hg/ml, P < .05), decreased the time constant of LV relaxation, increased the maximum rate of LV filling (37 +/- 19 ml/sec) (P < .05) and produced a downward shift of the early diastolic portion of LV pressure-volume loop. Pimobendan also augmented LV contractile performance during CHF exercise. In contrast, after CHF, amrinone no longer produced a positive inotropic effect. Amrinone improved LV relaxation and filling, both at rest and during exercise after CHF, but significantly less than pimobendan. We conclude that after CHF, the cardiac response to a PDE-III inhibitor is attenuated, but the response to Ca++ sensitizer is preserved. Thus, after CHF, pimobendan is more effective than amrinone in enhancing LV contractile state, LV relaxation and LV filling both at rest and during exercise.
Authors:
N Ohte; C P Cheng; M Suzuki; W C Little
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  282     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1997 Jul 
Date Detail:
Created Date:  1997-08-07     Completed Date:  1997-08-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  23-31     Citation Subset:  IM    
Affiliation:
Cardiology Section, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157-1045, USA.
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MeSH Terms
Descriptor/Qualifier:
Amrinone / pharmacology*
Animals
Dogs
Heart Failure / physiopathology*
Phosphodiesterase Inhibitors / pharmacology*
Physical Conditioning, Animal
Pyridazines / pharmacology*
Ventricular Function, Left / drug effects*
Grant Support
ID/Acronym/Agency:
HL42364/HL/NHLBI NIH HHS; HL45258/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Phosphodiesterase Inhibitors; 0/Pyridazines; 60719-84-8/Amrinone; 74150-27-9/pimobendan

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


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