DANTROLENE SODIUM REDUCES THE ENHANCED LEAKAGE OF CREATINE-KINASE CAUSED BY ETHANOL, COCAINE, AND ELECTRICAL-STIMULATION IN ISOLATED FAST AND SLOW MUSCLES OF RAT

Binge drinking of alcohol, cocaine overdose, or overexertion can lead to rhabdomyolysis characterized by elevated creatine kinase (CK) and m yoglobin in the serum, myoglobinuria, and muscle tenderness. Our previ ous studies showed that ethanol, cocaine, and electrical stimulation e nhanced the leakage of CK from isolated soleus and extensor digitorum longus (EDL) muscles of rat. Dantrolene sodium was reported to reduce the muscle damage and elevated serum CK levels in exercised rats. The present study was aimed at testing whether dantrolene can reduce the e nhanced leakage of CK from isolated rat soleus and EDL muscles caused by ethanol, cocaine, and electrical stimulation. After 4-hr incubation in oxygenated physiological solution at 37 degrees C, the mean leakag e of CK was 1.56 units/mg of muscle in soleus and 0.89 units/mg in EDL . Ethanol at 0.2% increased the leakage of CK by 47% (p < 0.05) in sol eus and by 26% in EDL. Cocaine at 1 mM increased the leakage of CK by 55% (p < 0.05) in soleus and by 27% in EDL. Electrical stimulation at 1 Hz for 4 hr increased the mean leakage of CK by 100% (p < 0.05) in s oleus and 127% (p < 0.05) in EDL. Dantrolene sodium reduced the enhanc ed leakage of CK caused by ethanol, cocaine, and electrical stimulatio n significantly in soleus and slightly in EDL. Dantrolene may involve myoplasmic free Ca2+ in these beneficial effects as in malignant hyper thermia, and may be useful in the treatment of rhabdomyolysis associat ed with acute alcoholic myopathy, cocaine overdose, and overexertion.