Effect of theophylline on calcium exchangeability in ventricular myocardium

The effects of theophylline on contractile force and myocardial calcium exchangeability were studied in isolated, electrically driven Langendorff perfused guinea-pig hearts. Following a 30-min exposure to 45Ca, total cellular calcium and 45Ca activity were measured in right ventricular samples. "Nontoxic" theophylline concentrations (5 x 10(-5) -10(-3) g/ml) which augmented contractile force without producing arrhythmias or contractures had no effect on total tissue calcium and did not alter the size of the fraction of cellular calcium exchangeable under steady-state conditions. A "toxic" concentration of theophylline (2 x 10(-3) g/ml) induced contractures and increased the amount of exchangeable cellular calcium. The latter effect was due to an increase in total calcium; the unlabelled cellular calcium fraction remained unchanged under the influence of all theophylline concentrations studied. The results suggest that theophylline increases the steady-state calcium exchangeability in ventricular myocardium only when the total calcium concentration is also increased.