Influence of pyruvate on economy of contraction in isolated rabbit myocardium

Abstract

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 P-adrenergic stimulation with isoproterenol. Results: Pyruvate (30 mM) increased developed force from 18.7 +/- 4.1 to50.8 +/- 12.1 mN/mm(2) (n= 10,p < 0.01). Force-time integral (FTI) increased by 329%, oxygen consumption assessed by diffusion-microclectrode technique increased from 2.86 +/- 0.30 mlO(2)/min 100 g to 6.28 +/- 1.28 mlO(2)/ min 100g(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 mu M) produced a comparable increase in developed force from 21.4 +/- 8.3 to 67.3 +/- 15 mN/mm(2) (n=7,p < 0.01),FTI increased only by 260% and MVO2 increased from 2.96 +/- 0.43 to 6.12 +/- 1.01 mlO(2)/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. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.