The terminally failing human myocardium exerts a negative force-frequency relationship (FFR), whereas a positive FFR occurs in nonfailing myocardium. To study the possibility of pharmacologically influencing this defect of the failing human heart, the the effect of halothane on the basal FFR and the FFR in the presence of isoproterenol and ouabain was investigated.Methods
Experiments were performed on isolated, electrically driven (0.5-2 Hz, 37 degrees Celsius, Calcium2+ 1.8 mmol/l) ventricular preparations. Myocardium from human failing and nonfailing hearts was obtained at cardiac surgery. To further characterize the studied myocardium, the positive inotropic effect of isoproterenol and the density of beta-adrenoceptors were measured using the radioligand sup 125 I-CYP.Results
Halothane produced a negative inotropic effect. The anesthetic (0.38 mmol/l) reversed the negative FFR in failing myocardium, antagonized the effect of isoproterenol (0.1 micro mol/l) on FFR, and restored the FFR in the presence of ouabain.Conclusions
Halothane restores the FFR in human failing myocardium possibly by influencing the intracellular Calcium2+ homeostasis. These findings provide evidence that pharmacologic interventions, e.g., during anesthesia, may influence contractility also as a result of a depressed or enhanced FFR.