Pyruvate potentiates inotropic effects of isoproterenol and Ca2+ in rabbitcardiac muscle preparations

Catecholamines and elevated extracellular Ca2+ concentration ([Ca2+](o)) au gment contractile force by increased Ca2+ influx and subsequent increased s arcoplasmic reticulum (SR) Ca2+ release. We tested the hypothesis that pyru vate potentiates Ca2+ release and inotropic response to isoproterenol and e levated [Ca2+](o), since this might be of potential importance in a clinica l setting to circumvent deleterious effects on energy demand during applica tion of catecholamines. Therefore, we investigated isometrically contractin g myocardial preparations from rabbit hearts at 37 degrees 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 (F-dev) from 1.89 +/- 0.42 to 3.62 +/- 0.6 2 (SE) mN/mm(2) (n = 8, P < 0.05) and isoproterenol (10(-6) M) alone increa sed F-dev from 2.06 +/- 0.55 to 25.11 +/- 2.1 mN/mm(2) (P < 0.05), whereas the combination of isoproterenol and pyruvate increased F-dev overproportio nally from 1.89 +/- 0.42 to 33.31 +/- 3.18 mN/mm(2) (P < 0.05). In a separa te series of experiments, we assessed SR Ca2+ content by means of rapid coo ling contractures and observed that, despite no further increase in F-dev b y increasing [Ca2+](o) from 8 to 16 mM, 10 mM pyruvate could still increase F-dev from 26.4 +/- 6.8 to 29.7 +/- 7.1 mN/mm(2) (P < 0.05, n = 9) as well as the Ca2+ load of the SR. The results show that the positive inotropic e ffects of pyruvate potentiate the inotropic effects of isoproterenol or Ca2 +, because in the presence of pyruvate, Ca2+ and isoproterenol induced larg er increases in inotropy than can be calculated by mere addition of the ind ividual effects.