© 2002 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Potentiation of beta-adrenergic inotropic response by pyruvate in failing human myocardium
Abteilung Kardiologie und Pneumologie, Georg-August-Universität Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, Germany
* Corresponding author. Tel.: +49-551-39-6351; fax: +49-551-39-8918 phermann{at}med.uni-goettingen.de
Background: Pyruvate has been shown to increase contractile function in isolated myocardium and to improve hemodynamics in patients with congestive heart failure. We tested the hypothesis that pyruvate potentiates the inotropic response to β-adrenergic stimulation and to elevated extracellular calcium, since this may be of potential therapeutic value in the clinical setting of acute heart failure in order to circumvent deleterious effects on energy demand as can occur during catecholamine therapy. Methods and Results: We investigated isometrically contracting isolated multicellular muscle preparations from terminal failing human hearts at 37°C, pH 7.4, and a stimulation frequency of 1 Hz. At an extracellular calcium concentration of 1.25 mM, pyruvate (10 mM) alone increased developed force (Fdev) from 9.0±2.3 to 21.1±4.3 mN/mm2 (n=9, P<0.001) and isoproterenol (1 µM) alone increased Fdev from 9.5±2.0 to 31.3±5.4 mN/mm2 (P<0.001), whereas the combination of pyruvate and isoproterenol increased Fdev over-proportionally from 9.0±2.3 to 47.4±6.4 mN/mm2 (P<0.01). In a separate series we assessed the combination of pyruvate and calcium. Although Fdev did not increase from 12 to 16 mM [Ca2+]o, 10 mM pyruvate further increased Fdev from 25.8±5.0 to 30.6±4.7 mN/mm2 (P<0.01). Rapid cooling contractures revealed that altered myofilament responsiveness and/or sarcoplasmic reticulum (SR) calcium load must underlie the positive inotropic effect of pyruvate. Conclusion: A combination of pyruvate and β-adrenergic stimulation may be of therapeutic value in acute heart failure by reducing the concentrations of potential deleterious catecholamines that are currently necessary to maintain adequate tissue perfusion.
KEYWORDS Heart failure; Adrenergic (ant)agonists; Calcium (Celular); Contractile function; Inotropic agents
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