Effects of increase in extracellular calcium on frequency-dependent inotropism in cardiac muscle

Frequency-dependent effects on contractility in isolated rabbit papillary muscles were compared at different calcium concentrations ranging between 1 and 12.5 mM. Increase in extracellular calcium up to 3 mM resulted in an increase in the frequency-dependent positive inotropy. A further increase in extracellular calcium, up to 5 mM, brought about a quantitative decrease in the frequency-dependent positive inotropy. Still higher concentrations of extracellular calcium, 7.5 and 12.5 mM, altogether abolished the frequency-dependent increase in contractility. The latter at these concentrations of calcium was rather depressed in response to frequency increases. These characteristic changes in the frequency-dependent inotropism at different extracellular calcium concentrations may have been due to the occurrence of a moderate to severe intracellular calcium overload. It is suggested that heart function in certain cardiac diseases, associated with intracellular calcium overload, may not improve with an increase in heart rate.