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This Article Full Text Full Text (PDF) All Versions of this Article: 290/2/H613    most recent 01219.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Savio-Galimberti, E. Articles by Ponce-Hornos, J. E. Search for Related Content PubMed PubMed Citation Articles by Savio-Galimberti, E. Articles by Ponce-Hornos, J. E.

Effects of caffeine, verapamil, lithium, and KB-R7943 on mechanics and energetics of rat myocardial bigeminies

Instituto de Investigaciones Cardiológica, School of Medicine, Universidad de Buenos Aires; Consejo Nacional de Investigaciones Científicas y Tecnicas; and Department of Biophysics, School of Dentistry, Universidad de Buenos Aires, Buenos Aires, Argentina

Submitted 3 December 2004 ; accepted in final form 26 July 2005

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 (H'_a) 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 ( = 101 ± 12.6%). Verapamil (an L-type Ca²⁺ channel blocker) decreased pressure maintenance of extrasystolic ( = 43.4 ± 3.7%) and postextrasystolic ( = 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 µM), inhibitors of the Na⁺/Ca²⁺ exchanger. Both agents decreased all mechanical responses, including postextrasystolic potentiation ( = 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.

postextrasystolic potentiation; paired-pulse stimulation; excitation-contraction coupling; calorimetry; sodium/calcium exchanger