Role of Calcium in Acute Hyperthermic Myocardial Injury

Hyperthermic Myocardial Injury. Introduction: We hypothesized that intracellular calcium overload may play an important role in heat‐induced myocardial injury. This postulate was investigated using a model of isolated guinea pig papillary muscle in which resting tension was measured as an indirect indicator of cytosolic free‐calcium concentration and the fluorescence changes of Fluo‐3 AM dye was measured as a direct indicator of cytosolic free‐calcium concentration. Methods and Results: Excised guinea pig right ventricular papillary muscles were attached to a force transducer in a high‐flow tissue bath and superfused with Tyrode's solution at 37°± 0.5°C. The temperature was rapidly changed to between 38.0° and 56.0°C for 60 seconds and then returned to 37.0°C. Hyperthermia caused a reversible increase in resting tension at temperatures between 45° and 50°C and irreversible contracture at ≥50°C. Rapid cooling contracture experiments and experiments measuring fluorescence of myocytes loaded with 5 μ M Fluo‐3 AM dye demonstrated that the hyperthermia‐induced rise in resting tension was likely due to an increase in intracellular calcium content. Inhibition of the sarcoplasmic reticulum calcium pump with 20 μ M thapsigargin resulted in irreversible contracture of the papillary muscles at temperatures between 45° and 50°C and significant increases in Fluo‐3 fluorescence at 48°C. Blockade of sarcolemmal calcium channels with 0.5 mM cadmium or 40 μ M verapamil did not attenuate the heat‐induced increase in resting tension and Fluo‐3 fluorescence. Conclusion: Hyperthermia causes an increase in resting tension of cardiac muscle that most likely is mediated by a calcium channel‐independent increase in calcium permeability of the sarcolemmal membrane and/or release of stored intracellular calcium.