Temperature modulates calcium homeostasis and ventricular arrhythmias in myocardial preparations

Objective: The aim was to evaluate the effect of temperature on reoxygenation induced ventricular arrhythmias in isolated hearts, on delayed after depolarisations and I-ti current in Purkinje fibres, and on sarcoplasmic reticular function and Ca2+ handling of single cardiac myocytes. Methods: Isolated guinea pig hearts were retrogradely perfused at 37 degrees C with a hypoxic medium for 15 min and reoxygenated for 10 min either at 33 degrees C or at 37 degrees C. Intracellular microelectrodes were used to assess the presence of delayed afterdepolarisations and triggered activity in sheep Purkinje fibres exposed to strophanthidin at different temperatures. I-ti current was evaluated in voltage clamp experiments. In rat cardiomyocytes, loaded with the fluorescent Ca2+ dye, indo-1, the sarcoplasmic reticular Ca2+ content was assessed at 30 degrees C and at 37 degrees C, either by a caffeine spritz puffed onto a cell from a patch pipette or by a post-rest contraction. Results: Hypothermic reoxygenation reduced the incidence of ventricular arrhythmias in isolated hearts (30%, n = 10, at 33 degrees C and 75%, n = 30, at 37 degrees C, p < 0.05). In Purkinje fibres, hypothermia decreased the amplitude of delayed afterdepolarisations. Moreover, at 32 degrees C, the amplitude of I-ti current was decreased to 59.2(SEM 2.6)% of the normothermic value [27.5(6.7) nA, n = 4, p < 0.005] and time to peak increased to 159.7(10.2)% [value at 37 degrees C = 470(41) ms, n = 4, p < 0.01]. In cardiac cells, sarcoplasmic reticular Ca2+ release induced by caffeine spritz or by post-rest contraction was increased at 30 degrees C. However, following a pacing period at 1 Hz, hypothermia prolonged the time to onset of the first spontaneous Ca2+ oscillation [59(14) s at 30 degrees C and 27(9) s at 37 degrees C, n = 5, p < 0.05] and reduced the oscillation frequency [1.1(0.4) min(-1) at 30 degrees C and 3.1(0.9) min(-1) at 37 degrees C, n = 5, p < 0.05]. Conclusions: Mild hypothermia increases sarcoplasmic reticular Ca2+ content but decreases the likelihood of spontaneous Ca release. This may explain the reduction of delayed afterdepolarisations and I-ti current amplitude in Purkinje fibres and it could represent a mechanism for the protection provided by hypothermia against ventricular arrhythmias.