Influence of perfusate calcium concentration on the inotropic insulin effect in isolated guinea pig and rat hearts

Abstract

Conflicting data on the inotropic effect of insulin are present in the literature suggesting a positive inotropic property or no inotropic effect or even a negative influence. To clarify the reason for these diverging findings, dose-response curves of insulin have been performed in isolated working rat and guinea pig hearts perfused with Krebs-Henseleit buffer containing 0.9, 1.25, 2.5, and 5 mM Ca²⁺ at 37 °C. At 1.25 mM [Ca²⁺], insulin (8 to 16 IU) regularly improved the inotropic state. LVdP/dt_max increased significantly from 1,900 to 2,300 mm Hg/s (+21 %) in guinea pig hearts and from 3,197 to 4,345 mm Hg/s (+36 %) in rat hearts. LVEDP did not change significantly. Myocardial oxygen consumption increased parallel with contractility. Heart rate was not influenced in either species. Coronary flow increased by 16.5 % in guinea pig hearts, but decreased in rat hearts by 13.6 % (p < 0.05 each). With 0.9 mM [Ca²⁺] the positive inotropic effect of insulin did not further augment. At 2.5 mM [Ca²⁺] insulin exhibited in both species no significant change of LVdP/dt_max but very high insulin doses depressed the heart. At 5 mM [Ca²⁺] insulin depressed the heart significantly already at lower concentrations. At 31 °C and 1.25 mM [Ca²⁺] the positive inotropic insulin effect was preserved. We conclude that the positive inotropic insulin effect in rat and guinea pig hearts depends on the extracellular [Ca²⁺], i.e., is maximal around 1.25 mM [Ca²⁺] and is reduced or absent at higher [Ca²⁺] or may even become negative.