Influence of pyruvate on economy of contraction in isolated rabbit myocardium

• Published in: European journal of heart failure Vol. 9; no. 8; pp. 754 - 761
• Main Authors: Keweloh, Boris, Janssen, Paul M.L., Siegel, Ulf, Datz, Nicolin, Zeitz, Oliver, Hermann, Hans-Peter
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-08-2007; Elsevier
• Subjects: Animals; Cardiotonic Agents - pharmacology; Dose-Response Relationship, Drug; energetics; Energy Metabolism - drug effects; Female; heart failure; In Vitro Techniques; Indoles - pharmacology; inotropic therapy; Isoproterenol - pharmacology; Myocardial Contraction - drug effects; Myocardium - metabolism; oxygen consumption; Oxygen Consumption - drug effects; pyruvate; Pyruvic Acid - pharmacology; Rabbits; Heart failure; Energetics; Pyruvate; Oxygen consumption; Inotropic therapy
• ISSN: 1388-9842; 1879-0844
• DOI: 10.1016/j.ejheart.2007.03.011

Background
Treatment of acute heart failure frequently requires positive-inotropic stimulation. However, there is still no inotropic agent available, which combines a favourable haemodynamic profile with low expenditure for energy metabolism. Pyruvate exhibits positive inotropic effects in vitro and in patients with heart failure. The effect on myocardial energy metabolism however remains unclear, but is meaningful in light of a clinical application.
Aims and methods
We investigated the influence of pyruvate on contractility and oxygen consumption in isolated isometric contracting rabbit myocardium compared to β-adrenergic stimulation with isoproterenol.
Results
Pyruvate (30 mM) increased developed force from 18.7±4.1 to 50.8±12.1 mN/mm2 (n=10, p<0.01). Force-time integral (FTI) increased by 329%, oxygen consumption assessed by diffusion-microelectrode technique increased from 2.86±0.30 mlO2/min*100 g to 6.28±1.28 mlO2/min*100 g (n=7, p<0.05). Economy of myocardial contraction calculated as the ratio of total FTI to oxygen consumption remained unchanged. In contrast, while isoproterenol (10 μM) produced a comparable increase in developed force from 21.4±8.3 to 67.3±15mN/mm2 (n=7, p<0.01), FTI increased only by 260% and MVO2 increased from 2.96±0.43 to 6.12±1.01 mlO2/min*100 g (n=7, p<0.01); thus, economy decreased by 23% (n=7, p<0.05).
Conclusion
Pyruvate does not impair economy of myocardial contraction while isoproterenol decreases economy. Regarding energy expenditure, pyruvate appears superior to isoproterenol for the purpose of positive inotropic stimulation.