RESUMEN
Binge drinking of alcohol, cocaine overdose, or overexertion can lead to rhabdomyolysis characterized by elevated creatine kinase (CK) and myoglobin in the serum, myoglobinuria, and muscle tenderness. Our previous studies showed that ethanol, cocaine, and electrical stimulation enhanced 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 enhanced 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 leakage 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 soleus 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 soleus and 127% (p < 0.05) in EDL. Dantrolene sodium reduced the enhanced leakage of CK caused by ethanol, cocaine, and electrical stimulation significantly in soleus and slightly in EDL. Dantrolene may involve myoplasmic free Ca2+ in these beneficial effects as in malignant hyperthermia, and may be useful in the treatment of rhabdomyolysis associated with acute alcoholic myopathy, cocaine overdose, and overexertion.
Asunto(s)
Cocaína/antagonistas & inhibidores , Creatina Quinasa/metabolismo , Dantroleno/farmacología , Etanol/antagonistas & inhibidores , Contracción Muscular/efectos de los fármacos , Fibras Musculares de Contracción Rápida/efectos de los fármacos , Fibras Musculares de Contracción Lenta/efectos de los fármacos , Animales , Permeabilidad de la Membrana Celular/efectos de los fármacos , Permeabilidad de la Membrana Celular/fisiología , Cocaína/farmacología , Técnicas de Cultivo , Estimulación Eléctrica , Etanol/farmacología , Masculino , Contracción Muscular/fisiología , Ratas , Rabdomiólisis/inducido químicamente , Rabdomiólisis/enzimologíaRESUMEN
Classic heat stroke is a disorder of thermal regulation that predominantly affects elderly patients during heat waves. In contrast to exertional heat stroke, rhabdomyolysis and myoglobinuric acute renal failure are considered to be unusual manifestations of classic heat stroke. We retrospectively reviewed the charts of seven patients admitted to Maimonides Medical Center with classic heat stroke over a 3-day period during a heat wave in July 1993. Three of these patients with classic heat stroke had rhabdomyolysis, but no renal failure; two completely recovered; and one had an ataxic gait disturbance. Three additional patients had rhabdomyolysis and myoglobinuric acute renal failure; one of them completely recovered, one survived with quadriplegia, and one died. Our findings suggest that rhabdomyolysis and myoglobinuric acute renal failure are common manifestations of classic heat stroke. Recognition of this complication warrants rigorous hydration and alkalinization of the urine to prevent or attenuate myoglobinuric acute renal failure.
Asunto(s)
Lesión Renal Aguda/etiología , Golpe de Calor/complicaciones , Rabdomiólisis/etiología , Anciano , Anciano de 80 o más Años , Creatina Quinasa/sangre , Creatinina/sangre , Femenino , Hematuria/etiología , Humanos , Masculino , Mioglobinuria/etiología , Pronóstico , Proteinuria/etiología , Estudios RetrospectivosRESUMEN
The present study was undertaken to evaluate the acute effects of ethanol on responses of the rat heart and skeletal muscles both in vivo and in vitro. In the anesthetized rat, intravenous infusion of ethanol at 0.1-0.5 g/kg body weight (33-167 mM) decreased the breathing rate by 8-83%, heart rate by 4-52%, and QRS amplitude by 5-27%, and increased the P-R interval by 1-49%. In the anterior tibialis muscle subjected to repetitive nerve stimulation at 100 Hz for 0.5 sec, ethanol at 0.1 g/kg increased the amplitude of the muscle action potential (AP) by 7%, whereas at 0.5 g/kg it decreased the muscle AP by 32%. The nerve-evoked tetanic tension was reduced by 7-34% at 0.1-0.5 g/kg ethanol. In the isolated rat heart, perfusion of ethanol at 0.1-3.0% (22-651 mM) decreased the heart rate by 8-48% and QRS amplitude by 10-39%, and increased the P-R interval by 5-61%. Left ventricular pressure was increased by 10% at 0.1% ethanol, and decreased by 80% at 3.0% ethanol. In the isolated rat phrenic nerve-diaphragm muscle preparation subjected to repetitive nerve stimulation at 100 Hz for 0.5 sec, 0.1-3.0% ethanol decreased the amplitude of the nerve AP by 5-89%, nerve-evoked muscle AP by 2-96%, and peak tetanic tension by 1-87%. On repetitive direct muscle stimulation at 100 Hz for 0.5 sec, 0.1-3.0% ethanol decreased the amplitude of the muscle-evoked muscle AP by 8-65%, and muscle-evoked tetanic tension by 2-65%. These studies indicate that ethanol causes smaller reduction in responses of the heart and skeletal muscles at clinical concentrations, but marked reduction in these responses at higher concentrations due to direct action on excitability of these tissues. At higher concentrations, ethanol causes greater reduction in excitability of the skeletal muscle than of the heart.
Asunto(s)
Electromiografía/efectos de los fármacos , Etanol/toxicidad , Sistema de Conducción Cardíaco/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Contracción Isométrica/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Electrocardiografía/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Binge drinking of alcohol may lead to acute alcoholic myopathy with rhabdomyolysis, which is characterized by skeletal muscle damage, elevated serum creatine kinase (CK), and myoglobinuria. This study was undertaken to test whether alcohol acts directly on the skeletal muscles to enhance the leakage of CK, and to assess the influence of fiber-type composition and repetitive contractions of the muscle on the effect of alcohol. After 4 hr of incubation in normal physiological solution at 37 degrees C, mean leakage of CK was 0.7 units/mg from isolated rat extensor digitorum longus (EDL), which has more fast-twitch glycolytic muscle fibers, and 1.2 units/mg from the soleus, which has more slow-twitch oxidative muscle fibers. Ethanol at 0.1, 0.2, and 0.5% concentrations caused significantly greater increase in leakage of CK from soleus than from EDL. In normal physiological solution, electrical stimulation at 1 Hz for 4 hr increased the leakage of CK by about the same degree in both EDL and soleus. In the presence of 0.1 and 0.2% ethanol, electrical stimulation markedly potentiated the alcohol-induced leakage of CK from both soleus and EDL. These results indicate that alcohol increases the leakage of CK by acting directly on skeletal muscle fibers, especially of the slow-twitch oxidative type, and that repeated muscle contractions potentiate the alcohol effect. These studies suggest that exercise may increase the chances of rhabdomyolysis in the alcoholics.
Asunto(s)
Creatina Quinasa/metabolismo , Etanol/farmacología , Contracción Isométrica/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Glucólisis/efectos de los fármacos , Glucólisis/fisiología , Contracción Isométrica/fisiología , Masculino , Músculo Esquelético/enzimología , Ratas , Ratas Sprague-DawleyRESUMEN
To assess the impairment of muscle membrane excitation, excitation-contraction (E-C) coupling, and contractility during muscle fatigue, we monitored the contracture responses of resting and fatigued muscles on exposure to high potassium and caffeine. On exposure to 140 mmol/L potassium, mouse extensor digitorum longus (EDL) developed a contracture which was 15.7% of tetanic tension before fatigue and 31.7% after fatigue, while soleus developed 59.4% contracture before and 68.8% after fatigue. Potassium causes contractures by depolarizing the muscle fiber membrane. Hence, membrane excitation is reduced in fatigued EDL and soleus. On exposure to 32 mmol/L caffeine, the contracture was 7.1% in resting EDL, 8.5% in fatigued EDL, 50.1% in resting soleus, and 43.7% in fatigued soleus. On exposure to 1 mmol/L caffeine followed by rapid cooling, the contracture was 3.0% in resting EDL, 3.2% in fatigued EDL, 21.5% in resting soleus, and 10.3% in fatigued soleus. Caffeine causes contracture by releasing Ca++ from the sarcoplasmic reticulum. Our results indicate reduced E-C coupling attributable to reduced membrane excitation in fatigued EDL, and reduced contractility in fatigued soleus.
Asunto(s)
Cafeína/farmacología , Contracción Muscular/efectos de los fármacos , Fatiga Muscular/efectos de los fármacos , Potasio/farmacología , Animales , Estimulación Eléctrica , RatonesRESUMEN
Fatigue mechanisms in normal intercostal muscle and muscle from patients with myasthenia gravis (MG) were evaluated by monitoring the compound muscle action potential (CMAP) and tetanic tension responses to repetitive nerve or muscle stimulation in vitro. When fatigue was induced by nerve stimulation at 30 Hz for 0.5 s every 2.5 s, about half of the original tension decreased after 30 min in normal muscle and 5 min in MG muscle. Analysis of the changes in area of CMAPs and tension indicated that impairment of neuromuscular transmission, muscle membrane excitation, and excitation-contraction (E-C) coupling and contractility accounted for 40%, 29%, and 31% of fatigue in normal muscle, and 83%, 0%, and 17% of fatigue in MG muscle. When fatigue was induced by muscle stimulation at 30 Hz, tension declined by a quarter after 30 min in normal muscle, but by a half after 17 min in MG muscle. Impairment of muscle membrane excitation and E-C coupling and contractility accounted for 58% and 42% of fatigue in normal muscle, and 22% and 78% of fatigue in MG muscle. Thus, fatigue of normal muscle is caused by impairment of at least four processes, and enhanced fatigue of MG muscle is caused by greater impairment of neuromuscular transmission, E-C coupling, and contractility.
Asunto(s)
Músculos Intercostales/fisiopatología , Miastenia Gravis/fisiopatología , Potenciales de Acción , Estimulación Eléctrica , Electromiografía , Fatiga/fisiopatología , Femenino , Humanos , Técnicas In Vitro , Músculos Intercostales/inervación , Músculos Intercostales/fisiología , Masculino , Persona de Mediana Edad , Contracción Muscular , Sistema Nervioso/fisiopatología , Factores de TiempoRESUMEN
Since patients with cocaine overdose were reported to develop rhabdomyolysis involving skeletal muscle damage leading to elevated levels of serum creatine kinase (CK), we determined whether cocaine can directly act on isolated rat skeletal muscles and increase the leakage of CK. In the fast-twitch muscle such as the extensor digitorum longus (EDL), following exposure to normal physiological solution for 1, 2, 3, and 4 hr, the mean leakage of CK was 0.6, 0.7, 0.9, and 1.2 units/mg of muscle respectively. On exposure of EDL to 0.1, 0.5, and 1.0 mM cocaine, there was no significant change in CK leakage. In the slow-twitch muscle such as the soleus, following exposure to normal physiological solution for 1, 2, 3, and 4 hr, the mean leakage of CK was 1.5, 2.2, 2.7, and 3.1 units/mg, which was significantly greater (P < 0.001) than in EDL at each time interval. On exposure of soleus to 0.1 mM cocaine, the CK leakage did not increase significantly, but on exposure to 0.5 mM cocaine, it significantly increased to 2.4, 3.4, 4.4, and 5.7 units/mg, and on exposure to 1.0 mM cocaine, it further increased to 2.7, 4.9, 6.5, and 7.6 units/mg. The CK activity of fresh muscle homogenate was 115.5 units/mg in EDL and 51.9 units/mg in soleus. These results indicate that cocaine can directly act on skeletal muscle and increase the leakage of CK especially from slow-twitch muscle like soleus, but not from fast-twitch muscle like EDL.