The force-frequency relationship in human heart failure: effect of pyruvate and isoproterenol

Martisiene I, Gendviliene V, Zablockaite D, Gurskaite H

Abstract

Purpose: The purpose of present study was to investigate the effect of metabolic substrate pyruvate and -adrenergic agonist isoproterenol and combination of these agents on the force- and relaxation-frequency relationship in human heart failure.
Material and methods: The experiments were performed on isolated human ventricle strips from patients undergoing cardiac corrective open heart surgery, using conventional method of registration of electromechanical activity. The stimulation frequency of myocardial strips was 0.2, 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 Hz.
Results: In control, i.e. at perfusion of myocardial strips by Tyrode solution and stimulation frequency 1 Hz, the contraction force (F) was 0.94±0.18 mN, half time of relaxation (tr) – 178.8±9.3 ms (n=12). Pyruvate (10 mmol/L) increased F to 176.0±13.4%, tr  – 104.6±3.1% (n=8, p<0.05) vs control. By the action of isoproterenol (10-5 mol/L) F increased to 122.1±10.2%, tr decreased to 58.9±3.1% (n=4, p<0.05) vs control. The relationship of F and tr from stimulation frequency in the absence of pyruvate and isoproterenol was negative. Pyruvate and isoproterenol didn’t alter the shape of force-frequency relationships but F was augmented at all stimulation frequencies. The positive inotropic effect of isoproterenol was potentiated by pyruvate. 
Conclusions: Pyruvate and isoproterenol alone can improve cardiac contractility in wide-range of stimulation frequency. The combination of these inotropic agents results in even more effective increase of contractile performance and therefore may be of therapeutic value in heart failure.

Key words: 	failing human myocardium; force-frequency relationship; pyruvate; isoproterenol.