Document Detail

Effects of caffeine, verapamil, lithium, and KB-R7943 on mechanics and energetics of rat myocardial bigeminies.
MedLine Citation:
PMID:  16055510     Owner:  NLM     Status:  MEDLINE    
We examined the effects of pharmacological alteration of Ca2+ sources on mechanical and energetic properties of paired-pulse ("bigeminic") contractions. The fraction of heat release that is related to pressure development and pressure-independent heat release were measured during isovolumic contractions in arterially perfused rat ventricles. The heat released by regular and bigeminic contractions showed two brief pressure-independent components (H1 and H2) and a pressure-dependent component (H3). We used the ratio of active heat (Ha') to pressure-time integral (PtI) and the ratio of H3 to PtI to estimate the energetic cost of muscle contraction (overall economy) and pressure maintenance (contractile economy), respectively. Neither of these ratios was affected by stimulation pattern. Caffeine (an inhibitor of sarcoplasmic reticulum function) significantly decreased mechanical responses and increased the energetic cost of contraction (delta = 101 +/- 12.6%). Verapamil (an L-type Ca2+ channel blocker) decreased pressure maintenance of extrasystolic (delta = 43.4 +/- 3.7%) and postextrasystolic (delta = 37.5 +/- 3.5%) contractions without affecting postextrasystolic potentiation, suggesting that a verapamil-insensitive fraction is responsible for potentiation. The verapamil-insensitive fraction was further studied in the presence of lithium (45 mM) and KB-R7943 (5 microM), inhibitors of the Na+/Ca2+ exchanger. Both agents decreased all mechanical responses, including postextrasystolic potentiation (delta = 67.3 +/- 3.3%), without altering overall or contractile economies, suggesting an association of the verapamil-insensitive Ca2+ fraction to the sarcolemmal Na+/Ca2+ exchanger. The effect of the inhibitors of the Na+/Ca2+ exchanger on potentiation suggests an increased participation of extracellular Ca2+ (and, thus, a redistribution of the relative participation of the Ca2+ pools) during bigeminic contractions in rat myocardium.
E Savio-Galimberti; J E Ponce-Hornos
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-07-29
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  290     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-11     Completed Date:  2006-02-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H613-23     Citation Subset:  IM    
Instituto de Investigaciones Cardiológica, School of Medicine, Universidad de Buenos Aires, Argentina.
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MeSH Terms
Caffeine / pharmacology*
Calcium / metabolism
Calcium Channel Blockers / pharmacology*
Electric Stimulation
Heart / physiology*
Intracellular Membranes / metabolism
Lithium Chloride / pharmacology*
Myocardial Contraction / drug effects,  physiology*
Rats, Wistar
Sodium-Calcium Exchanger / antagonists & inhibitors*,  metabolism
Thermogenesis / drug effects,  physiology
Thiourea / analogs & derivatives*,  pharmacology
Verapamil / pharmacology*
Reg. No./Substance:
0/2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; 0/Calcium Channel Blockers; 0/Sodium-Calcium Exchanger; 52-53-9/Verapamil; 58-08-2/Caffeine; 62-56-6/Thiourea; 7440-70-2/Calcium; 7447-41-8/Lithium Chloride

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

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