Document Detail

Positive inotropism and myocardial energetics: influence of beta receptor agonist stimulation, phosphodiesterase inhibition, and ouabain.
MedLine Citation:
PMID:  7954612     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: The aim was to study the effect of three positive inotropic interventions on myocardial force development and heat production in guinea pig papillary muscles in order to investigate the energetic consequences. METHODS: The positive inotropic agents used were epinine (beta adrenoceptor stimulation), E-1020 (phosphodiesterase inhibition), and ouabain (sodium-potassium ATPase inhibition). Heat measurements were accomplished using antimony-bismuth thermopiles, and initial heat was separated into tension dependent and tension independent heat using the butanedione-monoxime (BDM) and the shortening methods. RESULTS: Optimal concentrations of epinine, E-1020, and ouabain increased peak developed force from 20.0(SD 6.6) to 55.5(9.3) (n = 5; p < 0.01), from 20.9(9.1) to 27.2(7.2) (n = 6; p < 0.05), and from 23.4(9.2) to 44.9(18.0) (n = 6; p < 0.01), respectively. Epinine and E-1020 decreased the tension-time integral per unit initial heat, ie, the economy of isometric contraction, from 5.5(1.4) to 3.6(0.5) (p < 0.01) and from 5.5(1.4) to 3.1(0.9) N.m.s.J-1 (p < 0.01), respectively; no significant change was observed with ouabain [6.7(1.4) to 8.3(0.5) N.m.s.J-1]. The tension independent heat (calcium turnover) was measured in two different ways using BDM or shortening to abolish force production. It was increased significantly by epinine (by 141-243%), E-1020 (by 77-114%), and ouabain (by 23-38%). The first measurement in brackets is the BDM estimate, the second is the shortening estimate. From the tension-time integral and the tension dependent heat the crossbridge force-time integral was analysed: epinine and E-1020 decreased the crossbridge force-time integral from 0.46(0.16) to 0.31(0.06) pN.s (p < 0.01) and from 0.50(0.19) to 0.31(0.08) pN.s (p < 0.01), respectively, while ouabain left the force-time integral unchanged [0.59(0.27) to 0.63(0.20) pN.s]. CONCLUSIONS: (1) The inotropic effect of ouabain results from an increase in muscle activation with no change in crossbridge kinetics; (2) epinine and E-1020 increase the tension independent heat and decrease the crossbridge force-time integral, both effects reducing the overall economy; and (3) the shortening and BDM methods for measuring the tension independent heat give qualitatively similar but quantitatively different results.
C Holubarsch; G Hasenfuss; H Just; N R Alpert
Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Cardiovascular research     Volume:  28     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1994 Jul 
Date Detail:
Created Date:  1994-12-27     Completed Date:  1994-12-27     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  994-1002     Citation Subset:  IM    
Department of Physiology and Biophysics, University of Vermont, Burlington.
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MeSH Terms
Adrenergic beta-Agonists / pharmacology*
Deoxyepinephrine / pharmacology*
Guinea Pigs
Hot Temperature
Imidazoles / pharmacology*
Muscle Contraction / drug effects*,  physiology
Ouabain / pharmacology*
Papillary Muscles / drug effects,  metabolism*
Phosphodiesterase Inhibitors / pharmacology*
Pyridones / pharmacology*
Stimulation, Chemical
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Imidazoles; 0/Phosphodiesterase Inhibitors; 0/Pyridones; 119615-63-3/olprinone; 501-15-5/Deoxyepinephrine; 630-60-4/Ouabain

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