Ten patients, aged 39-61 years, with hypomagnesaemia due to chronic alcoholism (7 cases) or malabsorption (3 cases), have been investigated by assessing the maximum isometric voluntary contraction force (MVC) of the quadriceps femoris muscle (7 cases), laboratory screening (9 cases) and estimating the electrolyte and metabolite content of biopsy specimens from the quadriceps femoris muscle. The MVC ranged from 0.5 to 34 kp and was significantly lower than in 12 apparently healthy normomagnesaemic controls (p is less than 0.001). The results of the laboratory screening, apart from a significant lowering of the serum magnesium concentration (p is less than 0.01), were mainly within the range of normal values, apart from signs of liver damage, such as an elevated activity of S-OCT (3 cases), alkaline phosphatease(3 cases), S-ALAT (1 case) and an elevation of bilirubin and blood ammonia (2 cases). Low serum iron-binding capacity occurred in 4 cases, a finding reported in protein-calorie malnutrition. Muscle magnesium content was significantly lower than in healthy controls (p is less than 0.001). Muslce sodium and chloride contents were significantly increased (p is less than 0.05). Total H2O content and the extracellular H2O content were both significantly increased (p is less than 0.05). Pyruvate and lactate values were within the normal range. The apparent equilibrium constant for creatine kinase differed significantly ( is less than 0.01). ATP values were within the normal range, but there were slight decreases for ADP (p is less than 0.05) and creatine phosphate ( is less than 0.01), whcih is of interest in view of the lowering of the MVC and the diminished capacity for sustained muscular effort in hypomagnesaemic patients reported earlier.

The serum levels of myoglobin were measured in 106 male alcoholics. Subnormal levels were found in 31% of the alcoholics with no alcohol consumption for the last 2--4 weeks, while none of them had elevated levels. Of the alcoholics on ambulatory control and with varying current alcohol intake. 18% had increased levels compared to healthy controls. Serial myoglobin levels were determined in 19 patients following the cessation of heavy drinking sprees. Despite the fact that none of the patients had clinical evidence of acute myopathy, marked myoglobin elevations were noted in five patients; their serum levels gradually declined and normalized with 4--7 days. Comparing the three groups, similar frequencies of subnormal or elevated serum CK levels were observed. Myoglobin levels were not raised due to impaired glomerular filtration rates. No correlation was found between serum myoglobin and laboratory signs of liver affection. Although hypophosphatemia, hypomagnesemia and hypokalemia were occasionally noted, decreased serum electrolytes did not have any relation to elevated serum myoglobin. A transient, slightly increased urinary excretion of myoglobin parallel with increased excretion of beta 2-microglobulin was observed in 2/17 alcoholics, suggesting that instances of myoglobinuria in alcoholics with heavy recent drinking may be due to a transient minor tubular dysfunction.

The acute and chronic toxic effects of alcohol on skeletal and cardiac muscle are clinically important. Muscle weakness and atrophy are the main manifestations of skeletal myopathy, and arrhythmias and progressive left-ventricular dysfunction are those of cardiomyopathy. Most patients remain asymptomatic from these effects for a long time. Myocyte atrophy and death are the main pathological findings. A clear dose-related effect has been established with ethanol consumption, with gender and some specific gene polymorphisms being factors of increased susceptibility to alcohol-induced muscle damage. Pathogenic mechanisms are pleiotropic, the most relevant being disturbances in carbohydrate, protein, and energy cell turnover, signal transduction, and induction of apoptosis and gene dysregulation. Ethanol abstinence is the only effective treatment, although controlled drinking is useful in patients who do not achieve abstinence. Persistent high-dose consumption results in deterioration of muscle and heart function, with a high mortality due to arrhythmias and progression of heart failure.

The forearm ischemic exercise test (FIET) with serial lactate determinations is used worldwide for the screening of McArdle's disease and other glucogenosis. Yet there is no uniformity with regard to the intensity of the work and the ischemia time. The aim of this study was to standardize the test conditions in normal people and to check its efficacy in our population.

In a first stage, we included 9 healthy persons in whom four different conditions were applied regarding the cuff pressure and ischemia time. In a second stage, 5 previously known McArdle disease patients, 30 normal individuals and 25 patients with a diagnosis of myopathy other than glucogenosis underwent FIET with the conditions standardized in the first stage.

The best curve profile was obtained with a cuff pressure 20 mm Hg above systolic blood pressure and with exercise until fatigue o cramps without time limitation. With a cut-point at 200% of the basal values of ammonium and lactate, the sensitivity and specificity of FIET were 100% and 96%, respectively, for McArdle's disease. No major side effects were recorded in any case.

Conditions of FIET have been standardized. Taking into account the high sensitivity and specificity of the test, its use should be considered in the screening of anaerobic metabolic myopathies.

In the present study morphological changes occurring in the neuromuscular junctions (NMJ) of the extensor digitorum longus (EDL) and soleus muscles from albino rats (Rattus norvegicus) submitted to experimental chronic alcoholism were evaluated. Seventy two male animals aged 4 months and weighing on average 400g were divided into three groups: control, alcoholic and isocaloric. Six rats from each group were anesthetized and sacrificed after 5, 10, 15 and 18 months. The NMJ did not show detectable morphological changes in either muscle after treatment when examined by light microscopy. With respect to the dimensions, statistical analysis demonstrated a tendency to a statistically significant treatment x time interaction for the length of soleus muscle NMJ. The ultrastructural study, however, revealed that the NMJ of the soleus muscle of animals submitted to 18 months of experimental alcoholism presented important morphological alterations. Characteristically, the NMJ of these muscles is located on an elevation on the surface of the muscle fiber, presenting a regular round, oval or elliptical shape and continuous and not very deep synaptic grooves. Approximately 30% of the NMJ of alcoholic rats are irregular in shape, with the sarcolemmal elevations typical of the synapse region being flattened on at least one side, with discontinuous synaptic grooves, and deep and punctiform contacts of the synaptic buds. These data suggest that, although skeletal muscle has a greater natural resistance against the direct or indirect effects of alcohol, some submicroscopic morphological alterations are detectable in the NMJ, especially in muscles with oxidative metabolism (soleus) following long periods of ingestion of alcohol.

To report a possible association between naltrexone therapy and the development of rhabdomyolysis in one patient.

A 28-year-old white man in good physical health was started on naltrexone 50 mg/d for inpatient treatment of alcohol dependence and depression. A routine serum chemistry panel obtained on day 9 of naltrexone therapy showed marked new elevations in creatine kinase and aspartate aminotransferase. The patient remained asymptomatic and did not develop renal insufficiency. The serum enzyme concentrations returned to normal within eight days of naltrexone discontinuation.

Rhabdomyolysis has not been previously reported to occur in patients during treatment with naltrexone. Alcoholism may result in a reversible acute muscle syndrome, but our patient did not fit the appropriate clinical profile for such a syndrome. Additionally, the other prescribed medications could not be implicated as possible causative agents.

This case report illustrates a possible association between naltrexone therapy and rhabdomyolysis.

We previously examined the effect of alcohol on muscle energy metabolism in chronic alcoholics by using 31P-magnetic resonance spectroscopy. Measurements of intracellular pH and PCr index [PCr/(PCr + Pi)] during resting, hand grasping, and recovery in the left flexor digitorum superficialis muscle of alcoholics with neurological signs showed a marked decrease and delayed recovery of pH, but rapid recovery of PCr index indicating that the muscle produces lactate during and after exercise to maintain the ATP level. To clarify the reason for this preference for anaerobic metabolism, we conducted simultaneous measurements of the muscle blood supply during and after exercise by using the near-infrared light method and energy metabolism by using 31P-magnetic resonance spectroscopy. In alcoholics with neurological signs, we observed a significant increase of oxyhemoglobin after exercise with a slight increase of total hemoglobin. In healthy volunteers and chronic alcoholics without neurological signs, such an overshoot of oxyhemoglobin was not observed. We conclude that chronic alcoholics with neurological signs have an abnormality of aerobic metabolism owing to muscle mitochondrial dysfunction.

Magnetic resonance imaging (MRI) of thigh and leg muscles was performed in a patient with alcoholic myopathy showing myalgia, hypercreatine kinasemia, and hypermyoglobinemia. High signal intensities in both T1- and T2-weighted images were widely distributed in the affected muscle groups, which most likely reflected lipid accumulation. Although he had hypermyoglobinemia, MRI and muscle biopsy did not show findings of rhabdomyolysis, such as necrosis, regeneration, and edema. We suggest that the high signal intensities in this case may have indicated "prerhabdomyolysis" related to alcohol abuse and that muscle MRI is useful in the evaluation of alcoholic myopathy, mainly predicting the onset of rhabdomyolysis.

Authors present the case of a 37-year-old man admitted to the emergency room of Universidade Federal de São Paulo-Escola Paulista de Medicina, with hyperosmolar coma, following progressive muscle discomfort and loss of renal function, with further need of dialysis therapy. Initial laboratory evaluation showed marked hyperglycemia, hypernatremia, hyperosmolarity, and high levels of creatinine. In the evolution he presented an elevation of creatino-phosphokinase levels in parallel with increasing levels of urea and creatinine. Urinalyses showed progressive increase in proteinuria and hematuria. A muscle biopsy was performed and confirmed the presence of muscular necrosis. The purpose of this paper is to emphasize hyperosmolarity as a newly described cause of rhabdomyolysis. The authors point out its multifactorial physiopathology and also stress the relatively common occurrence of acute renal failure (ARF) following an episode of rhabdomyolysis, and the poor prognosis that this complication represents.

The effects of chronic alcoholism on gastrocnemius muscle of well-nourished mice were morphologically studied to test the direct toxic role of ethanol on skeletal muscle. Thirty male young adult C57BL10 mice were divided in two groups: Group A (control) consisting of ten mice that drank water and Group B (alcoholic) consisting of twenty mice that drank 25% ethanol. All mice were allowed a balanced laboratory chow. The animals were kept on this ad libitum regimen under the same conditions of environment for 48 weeks and were weighed once a week. The daily dietary consumption and caloric intake were estimated, the animals having had a substantial weight gain, showing no signs of malnutrition. At the end of the experiment the animals were killed for morphological studies. No abnormalities were observed by conventional microscopy. Striking deviations from normal were verified by electron microscopy in all specimens. Dilatation of sarcoplasmic reticulum was a common feature, sometimes resulting in the formation of large vesicles and involving the terminal cisternae with the displacement of the triads. Areas of narrowing, splitting and loss of myofibrils were seen. Zones of complete disorganization of miofibrils could be occasionally observed. Mitochondria were generally normal. Peculiar tubular aggregates seen commonly in periodic paralysis and other human pathological conditions, were encountered in both control and alcoholic mice. Intramuscular nerves and neuromuscular junctions were normal. Important abnormalities in muscle capillaries were observed, consisting of swelling of endothelial cells and thickening of the basal lamina. A diffuse microvesicular lipid infiltration was seen in the cytoplasm of the hepatocytes which seems to be a further evidence of the toxic role played by ethanol. We concluded that prolonged ingestion of ethanol, representing 14.4% of total calories, produces in the gastrocnemius muscle of well-nourished C57BL10 mice a distinct spectrum of ultrastructural changes which reflects a direct toxic effect on the skeletal muscle. These alterations are similar to those described in human chronic alcoholic myopathy.

To determine the effect of alcohol on carbohydrate metabolism, 48 human muscle biopsies from chronic alcoholics were studied. The level of glycogen and the activities of the enzymes catalyzing glycogen and glucose metabolism were analyzed. Chronic alcohol intake produced an increase in glycogen concentration and a decrease in pyruvate kinase activity before the first signs of myopathy appeared. When myopathy was present, glycogen decreased. These changes may contribute to the decline in skeletal muscle performance in these patients.

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.

Repeated and excessive consumption of alcohol leads to pathophysiological disorders in skeletal muscles. A successful management of this syndrome requires a strict abstinence and a nutritionally adequate diet. We propose here a simple and noninvasive investigation using 31P magnetic resonance spectroscopy (MRS) to monitor the recovery of the basal energy status of eminence thenar muscles from documented chronic alcoholic patients during a controlled 15-day period of abstinence. Cessation of alcohol abuse induced a significant recovery of the PCr/(PCr+P(i)) ratio otherwise depressed before the abstinence. On the contrary, the relative level of free inorganic phosphate decreased, whereas intracellular pH was not affected. These results demonstrate (a) the rapid improvement of basal muscular energy metabolism during abstinence for patients with a chronic and heavy alcohol consumption, and (b) the feasibility of a follow-up of this recovery by serial examinations using 31P MRS.

Chronic ethanol feeding in the rat is associated with a skeletal myopathy involving primarily type-II muscle fibres, which is recognised to be mediated via a specific impairment in protein turnover. This paper investigates whether the cause of this myopathy may be related to abnormalities in carbohydrate and lipid metabolism in different muscles. [U-14C]Glucose metabolism was examined in two muscles with different fibre compositions, the extensor digitorum longus (EDL) muscle, which contains predominantly type-II muscle fibres, and the soleus muscle, which is composed primarily of type-I muscle fibres. Feeding on the ethanol-supplemented Lieber-DeCarli liquid diet for 2 or 6 weeks was associated with profound disturbances in glucose metabolism in both EDL and soleus muscles, particularly in relation to rates of glycogen and alanine formation. We discuss the importance of these metabolic changes in relation to the genesis of chronic alcoholic skeletal myopathy.

Increased Na+,K+-ATPase activity observed after chronic ethanol consumption has been examined to determine whether the increase is due to changes in the kinetic properties of the enzyme or increases in the amount of enzyme in the membranes examined. In skeletal muscle and erythrocyte ghosts from rat, as well as from humans, increased Na+,K+-ATPase activity in ethanol-consuming individuals was not accompanied by an increase in the number of ouabain binding sites. In studies with intact human erythrocytes, similar ouabain-sensitive 22Na+ and 86Rb+ pumping rates were observed between normal and ethanol-consuming individuals and the Na+ to Rb+ pumping ratio was found to be 1.5 in all cases. However, ouabain-sensitive lactate plus Pi formation was increased in cells from alcoholic individuals. Thus these data suggest that increased enzyme activity may be due to a kinetic alteration of the Na+,K+-ATPase and that the enzyme may be less efficient in coupling ion pumping to ATP hydrolysis than the enzyme in normal cells.

Twenty-two chronic alcoholic patients were assessed by neurologic examination and muscle biopsy. The patients manifested proximal muscular weakness to a variable extent. One case presented as an acute bout of myopathy, according to the Manual Muscle Test, MMT. The most prominent histologic feature observed was muscle atrophy (95.3%) better evidenced through the ATPase stain with the predominance of type II A fibers (71.4%). Lack of the mosaic pattern (type grouping) seen in 76% of the cases and an important mitochondrial proliferation with intrasarcoplasmatic lipid accumulation in 63% of the patients. In case of acute presentation of muscle weakness the pathological substrate is quite different, i.e. presence of myositis mainly interstitial characterized by lymphoplasmocytic infiltrate and several spots of necrosis like Zencker degeneration. Based on histologic criteria, our data suggest that: the main determinant of muscle weakness seen in chronic alcoholic patients is neurogenic in origin (alcoholic polyneuropathy); the direct toxic action of ethanol under the skeletal muscle is closely related to the mitochondrial metabolism; the so-called acute alcoholic myopathy has probably viral etiology.

Striated musculature is considered unusually tolerant to all kinds of injuries, and rhabdomyolysis associated with drug overdose or chronic drug intake is a rare event. This may be because striated musculature, in contrast to other tissues such as liver and kidney, shows little affinity for most drugs. Several different types of drug-induced rhabdomyolysis may be distinguished, and the clinical features of the condition may vary widely, from moderate myalgia to involvement of groups of muscles to involvement of the total skeletal musculature. In clinically asymptomatic rhabdomyolysis, early diagnosis is only made if routine laboratory tests include determination of serum creatine kinase. Determination of myoglobin in serum and urine is more sensitive and allows earlier diagnosis of muscle necrosis. Myoglobinaemia may lead to toxin-induced tubular necrosis, and impairment of renal function or even acute renal failure. About 10% of all cases of acute renal failure are due to rhabdomyolysis. Fulminant rhabdomyolysis may be associated with excessive hyperkalaemia and hypocalcaemia which may induce further life-threatening complications. Therefore, early diagnosis of rhabdomyolysis is most important for prevention of its potentially life-threatening sequelae. Therapy of rhabdomyolysis consists of supportive and specific measures. Early diagnosis may help to prevent life-threatening sequelae like acute renal failure, electrolyte imbalance and shock. Withdrawal of the incriminated drug or detoxification in drug overdose should be followed by supportive measures including infusion therapy and correction of dehydration and electrolyte imbalances. Forced diuresis with sodium bicarbonate may protect the kidney function from acidosis and precipitation of myoglobin in tubules. Elimination of myoglobin from plasma may be enhanced by plasmapheresis. In patients with acute renal failure, haemodialysis is necessary. In malignant hyperthermia, immediate infusion of dantrolene sodium is required. This drug also seems to have a beneficial effect in neuroleptic malignant syndrome. The repair mechanisms of striated musculature function extremely well. The prognosis of muscular atrophy after the acute stage of rhabdomyolysis is excellent. The same is true for the prognosis of acute renal failure. However, the extent of complications or survival of the acute stage of rhabdomyolysis strongly depend on early diagnosis and start of adequate therapy.

Despite the well known effects of chronic alcohol abuse on the gastrointestinal, cardiovascular, nervous and endocrine systems, little information is available on its effect on renal function. To assess renal function we measured urinary excretion of albumin, alpha 1 microglobulin and retinol binding protein in 30 chronic alcoholic patients. Our data shows that 40% of chronic alcoholic patients have impaired renal tubular function.

To determine the prevalence of alcoholic myopathy and cardiomyopathy, we studied a group of 50 asymptomatic alcoholic men (mean age, 38.5 years) entering an outpatient treatment program. Studies performed included an assessment of muscle strength by electronic myometer, muscle biopsy, echocardiography, and radionuclide cardiac scanning, with comparison to healthy control subjects of similar age. The patients' mean (+/- SEM) daily alcohol consumption was 243 +/- 13 g over an average of 16 years. These patients had no clinical or laboratory signs of malnutrition or electrolyte imbalance. Forty-two percent of the patients, as compared with none of the controls, had strength of less than 20 kg as measured in the deltoid muscle. Muscle-biopsy specimens from 23 patients (46 percent) had histologic evidence of myopathy. In the cardiac studies, when the alcoholic patients were compared with 20 healthy controls, the patients had a significantly lower mean ejection fraction (59 vs. 67 percent), a lower mean shortening fraction (33 vs. 38 percent), a greater mean end-diastolic diameter (51 vs. 49 mm), and a greater mean left ventricular mass (123 vs. 106 g per square meter of body-surface area). One third of the alcoholics had an ejection fraction of 55 percent or less, as compared with none of the controls. Endomyocardial biopsy specimens from six patients with ejection fractions below 50 percent showed histologic changes of cardiomyopathy. The estimated total lifetime dose of ethanol correlated inversely with muscular strength (r = -0.65; P less than 0.001). In an analysis that also included six patients with symptomatic alcoholic cardiomyopathy, the estimated total lifetime dose of ethanol correlated inversely with the ejection fraction (r = -0.58; P less than 0.001) and directly with the left ventricular mass (r = 0.59; P less than 0.001). We conclude that myopathy of skeletal muscle and cardiomyopathy are common among persons with chronic alcoholism and that alcohol is toxic to striated muscle in a dose-dependent manner.

Myocardial and skeletal muscle impairment caused by alcohol has been thoroughly studied. Nevertheless, the simultaneous involvement of those tissues by ethanol has not been broached in medical literature. We have studied ten patients undergoing alcoholic cardiomyopathy. They were subjected to a detailed neurological examination, muscle enzymes serum level determinations, electromyography, and muscle biopsy with analysis of the tissue by usual histological techniques and by electron microscopy. Only one of ten patients exhibited proximal weakness and atrophy of the lower limbs, the electromyographic and histological findings correlating with the clinical feature of the chronic muscle disease due to alcohol consumption. The electromyographic findings included muscle disease in eight patients, neuron disease in one patient and no changes at all in the tenth patient. In one patient only, the skeletal muscle proved normal when examined by conventional histological techniques. In the other nine patients there were several minimal changes, such as the proliferation of nuclei beneath the sarcolemma, atrophy of fibers, hyalinization, vacuolation, loss of muscle fiber striae, and atrophy of groups of fibers. Electron microscopy demonstrated the following changes in nine patients: intracellular edema, dissociation of myofilaments, alteration of the Z line, changing in the shape and increase in the number of mitochondria, thickening of sarcolemma, and vacuolation and increase of the glycogen granules. Since all patients exhibited skeletal muscle injury, we concluded that there is a close relation between alcoholic cardiomyopathy and skeletal muscle disease.

Malignant hyperthermia is a hereditary trait characterized by hypercatabolic reactions induced by anesthetic drugs, or physical or emotional stress. Patients must be treated quickly and efficiently in order to prevent irreversible organ damage and death.

The forearm ischemic exercise test (FIET) is a very important clinical tool for evaluation of patients suspected to have a metabolic disorder of muscle function. Failure to elevate lactate in blood washed out from ischemically exercised muscles confirms an abnormality of glycolytic metabolism. A normal increase of lactate on FIET is assumed to rule out a disorder of glycolytic metabolism. Two patients with low levels of muscle phosphorylase are presented who produced a normal elevation of lactate on FIET. This suggests that, although the FIET is capable of identifying patients with absence of myophosphorylase, the test cannot identify patients with a partial expression of that disorder. Evaluation of the blood samples for ammonia in addition to lactate can be a significant help in confirming that the exercise performed by the patient was an adequate challenge for the glycolytic pathway. In addition, failure to elevate ammonia on ischemic exercise can identify a relatively new disorder of muscle metabolism.

A sample of 200 men from the general population was investigated concerning alcohol consumption in relation to laboratory findings. The relation between symptoms of alcoholism (subjective relative loss of control over drinking, blackouts and morning drinks) and the alcohol consumption was also studied. The subjects were divided into three groups: (1) a group with low alcohol consumption without symptoms of alcoholism, (II) an intermediate group with low, moderate or high alcohol consumption and one or more alcohol symptoms and (III) a heavy-drinking group with two or more symptoms. The heavy-drinking group had significantly higher serum bilirubin, aspartate amino-transferase (ASAT), creatine kinase and lactate dehydrogenase values than the other two groups. Gamma-glutamyl transpeptidase (GGT) showed no relation to alcohol consumption. The use of liver-metabolized drugs was investigated. Ten of the 53 heavy drinkers were taking such drugs, because of illness, and the other 43 were not. The heavy drinkers taking drugs showed pathological laboratory values throughout, in contrast to the subjects of the other subgroups. Serum GGT was high in the drug-using groups but was not significantly elevated in the groups taking only alcohol and no drugs.

This chapter reviews the disturbances of the serum sodium and potassium concentrations, acid-base imbalances, and acute renal dysfunction that are seen frequently in alcoholic patients. The hyponatremia common in decompensated cirrhotics is caused by an impairment of renal free water clearance and concomitant water ingestion. Excessive proximal renal tubular sodium reabsorption and nonosmotic vasopressin release underlie the defect in renal water excretion in cirrhosis. Restriction of water intake is the principal therapeutic measure for hyponatremia. Hypokalemia is common in alcoholics but when observed does not always represent true potassium depletion. Although most cirrhotics have a diminished total body potassium content, intracellular potassium concentration is usually normal. In some patients gastrointestinal and renal potassium losses and nutritional potassium deficiency may cause true potassium depletion. Respiratory and metabolic alkalosis are the acid-base disturbances seen most frequently in alcoholics. Acidosis is relatively uncommon and is usually due to renal insufficiency, lactic acid or keto-acid accumulation. Toxin ingestion (methanol, ethylene glycol, or isopropanol) may also cause severe acidosis. Rhabdomyolysis, common in severe alcoholism, may produce various electrolyte disturbances and acute renal failure. The prognosis for recovery is good although temporary dialysis may be necessary.

Although musculoskeletal symptoms are common in alcoholics, little is known of the prevalence of muscle pathology in this group. Quadriceps muscle biopsies were performed in 151 alcoholics (105 men). Ninety patients showed type 2 fibre atrophy predominantly affecting the type 2b anaerobic glycolytic fibres. In contrast, 7 biopsies revealed some muscle necrosis and only 1 patient had acute rhabdomyolysis. Amongst those alcoholics with muscle atrophy the quantity of alcohol consumed in the year prior to biopsy correlated significantly with the severity of the atrophy. Atrophy was not associated with vitamin B12, folate, pyridoxine, riboflavin or thiamine deficiencies. Although patients with severe liver disease, peripheral neuropathy or malnutrition were more likely to have muscle atrophy, nerve conduction studies showed that atrophy and neuropathy each occurred independently. Sequential studies in abstaining alcoholics showed a significant improvement within 3 months and often complete recovery within a year. Continued consumption of alcohol was associated with persistence or progression of the atrophy. This study shows that reversible type 2b muscle fibre atrophy is a frequent finding in alcoholics and suggests that it is directly related to alcohol consumption and is not a consequence of malnutrition, vitamin deficiency or peripheral neuropathy.

The histochemical features of muscle injury and repair were examined in an experimental form of acute alcoholic myopathy in the rat. Typical features of rhabdomyolysis were found, which were indicated by scattered muscle fiber necrosis followed by sequential phases of fiber degeneration, phagocytosis, and regeneration. Nests of small, regenerated, or split fibers remained 2 months after the episode of acute myopathy. Vulnerability of type 1 fibers to alcohol-induced muscle injury was evident by selective involvement of muscles with type 1 fiber predominance and by the fact that regenerating fibers were virtually exclusively type 1. The histologic features of myopathy in this model closely parallel those in human acute alcoholic myopathy.

Three patients with opiate self-poisoning developed acute muscle damage with elevated serum aspartate aminotransferase and creatine kinase activities, increased serum myoglobin concentrations, raised plasma creatinine concentrations, hypocalcaemia and hyperphosphataemia. These abnormalities gradually resolved over 7-10 days, but recovery was complicated due to the development of acute renal failure (requiring haemodialysis) in one patient. Plasma drug concentrations, shortly after admission, in the patients taking dihydrocodeine and morphine were grossly elevated (184 and 60 micrograms/l respectively). Clinical evidence of myopathy was minimal in all three patients and muscle biopsy of one patient was normal at 7 days.

Acute alcoholic myopathy, a syndrome of sudden muscle necrosis, occurs as a result of binge drinking, whereas chronic alcoholic myopathy is a more indolently evolving syndrome of proximal weakness and muscle atrophy that accompanies prolonged alcohol abuse. The characteristic features and management of these disorders are highlighted.

The biochemistry, pharmaco-kinetics, and pathophysiology of alcohol and alcoholism are reviewed and approaches to the clinical management of coma, alcohol withdrawal, and anaesthesin are considered.

Muscles of the lower legs of rats given 25% ethanol in water ad libitum for up to 9.5 months were studied using histological, histochemical and electrophysiological techniques. Ethyl alcohol was substituted for about 20% of the total calorific input of the animals. The observations were compared with the structure of the gastrocnemius muscle of five alcoholics with clinical neuropathy. Fibrillation potentials and angulated atrophic fibers were observed in the muscles of animals on alcohol for 9.5 months. No fiber type grouping was present. There was also phagocytosis of the muscle fibers and changes in their internal structure, as reflected by the distribution of NADH-diaphorase. The observed muscle changes in the alcoholics and those in the experimental animals on alcohol differed mainly quantitatively, the only exception being the presence of fiber type grouping in the biopsies from the alcoholics.

Several studies have suggested that muscle lactic acid production is defective in alcoholic myopathy. However, normal controls have not been evaluated. To study the effects of ethanol on the production of lactic acid in normal exercised muscle, oral ethanol (1 g per kg body weight, 20% v/v) was given to eight nonalcoholic subjects. Forearm ischemic exercise with a total work load of 7.2 kg-m/min was performed just before and 90 min after ingestion of ethanol. At the time of exercise, the serum ethanol level was 95.7 +/- 15.1 mg% (mean +/- SD). Resting serum lactic acid was significantly higher after ingestion of ethanol (15.7 +/- 4.5 mg%) than before (8.5 +/- 4.7 mg%). Lactic acid generation with ischemic exercise was significantly lower after ethanol ingestion. The mean peak serum lactic acid level (expressed as percentage elevation above resting) was 330.5 +/- 118.2% before and 127.9 +/- 75.1% after (p less than .05). These results indicate that a single oral dose of ethanol decreases lactic acid production by exercised muscle in normal subjects.

Myoglobin is the oxygen-binding protein characteristic of skeletal and cardiac muscle. With muscle disease or dysfunction, myoglobin may enter the circulation, and after renal clearance, it may also appear in the urine. Therefore, the presence of myoglobinemia and myoglobinuria may serve as indicators of the presence and severity of muscle disease. With newly developed methods of detection, myoglobinemia and myoglobinuria are now recognized as complications of trauma, ischemia, surgery, states of exertion and stress, metabolic abnormalities, inherited enzyme disorders, toxin and drug actions, and inflammatory states. Infarction of the heart muscle also can be detected by myoglobin assay. Persistent myoglobinuric states may be complicated by renal failure and electrolyte imbalance. The diagnosis of myoglobinemia and myoglobinuria can be now confirmed with the use of immunoassay techniques. Although not yet widely available, they offer the possibility of the specificity and sensitivity needed for clinical use.

Electrophysiological and pathological studies have been performed on three patients with recurrent focal swelling of the calf muscles simulating deep venous thrombosis, and in a patient with both cardiomyopathy and skeletal muscle disease. In all patients there were elevated CPK levels, histological evidence of an acute myopathy, heavy alcohol intake prior to the development of symptoms, and improvement in hospital with the cessation of alcohol consumption. These patients illustrate a form of alcoholic muscle disease which may be more common than generally realised.