Role of calcium in acute 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-calci...
| Publicado en: | Journal of Cardiovascular Electrophysiology Vol. 12; no. 5; pp. 563 - 570 |
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| Autores principales: | , , , , , |
| Formato: | Journal Article |
| Publicado: |
Wiley-Blackwell
May2001
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| Acceso en línea: | Ver este registro en EBSCOhost |
| Sumario: | 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 hath 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 [mu]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 [mu]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 [mu]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. |
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