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Abteilung für Kardiologie und Pneumologie, Universität Göttingen, D-37075 Göttingen, Germany
Catecholamines and elevated extracellular Ca2+
concentration ([Ca2+]o) augment contractile
force by increased Ca2+ influx and subsequent increased
sarcoplasmic reticulum (SR) Ca2+ release. We tested the
hypothesis that pyruvate potentiates Ca2+ release and
inotropic response to isoproterenol and elevated [Ca2+]o, since this might be of potential
importance in a clinical setting to circumvent deleterious effects on
energy demand during application of catecholamines. Therefore, we
investigated isometrically contracting myocardial preparations from
rabbit hearts at 37°C, pH 7.4, and a stimulation frequency of 1 Hz.
At a [Ca2+]o of 1.25 mM, pyruvate (10 mM)
alone increased developed force (Fdev) from 1.89 ± 0.42 to 3.62 ± 0.62 (SE) mN/mm2 (n = 8, P < 0.05) and isoproterenol (10
6 M)
alone increased Fdev from 2.06 ± 0.55 to 25.11 ± 2.1 mN/mm2 (P < 0.05), whereas the
combination of isoproterenol and pyruvate increased Fdev
overproportionally from 1.89 ± 0.42 to 33.31 ± 3.18 mN/mm2 (P < 0.05). In a separate series of
experiments, we assessed SR Ca2+ content by means of rapid
cooling contractures and observed that, despite no further increase in
Fdev by increasing [Ca2+]o from 8 to 16 mM, 10 mM pyruvate could still increase Fdev from 26.4 ± 6.8 to 29.7 ± 7.1 mN/mm2
(P < 0.05, n = 9) as well as the
Ca2+ load of the SR. The results show that the positive
inotropic effects of pyruvate potentiate the inotropic effects of
isoproterenol or Ca2+, because in the presence of pyruvate,
Ca2+ and isoproterenol induced larger increases in inotropy
than can be calculated by mere addition of the individual effects.
contractility; sarcoplasmic reticulum; energetics; myocardium; 
-adrenergic stimulation; trabeculae
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