Severe weakness requiring prolonged rehabilitation and abnormal clinical neurologic findings are extremely common in survivors of protracted critical illness. Neurophysiologic evidence of chronic partial denervation of muscle consistent with previous critical illness polyneuropathy is almost invariable and can be found up to 5 yrs after intensive care unit discharge in >90% of these long-stay patients. Evidence of myopathy is unusual. These findings have important implications for the management and rehabilitation of intensive care survivors.

Neurophysiological abnormalities complicating critical illness can be broadly divided into three types -- sensory abnormalities alone, a pure motor syndrome and a mixed motor and sensory disturbance. The motor syndrome could be explained by an abnormality in the most distal portion of the motor axon, at the neuromuscular junction or the motor end plate and, in some cases, by inexcitable muscle membranes or extreme loss of muscle bulk. The mixed motor and sensory disturbance which is characteristic of 'critical illness polyneuropathy' could be explained by a combination of the pure motor syndrome and the mild sensory neuropathy. More precise identification of the various neurophysiological abnormalities and aetiological factors may lead to further insights into the causes of neuromuscular weakness in the critically ill and ultimately to measures for their prevention and treatment.

The present study was conducted to investigate the metabolic regulation of the oxidation of branched-chain amino acids (BCAA) by exercise in human skeletal muscle. Five trained male volunteers were exercised on a cycle ergometer at 70% +/- 10% (mean +/- SD) of their maximal oxygen consumption (VO2max). Percutaneous quadriceps muscle biopsies were obtained under local anaesthesia at rest and after 30 and 120 min of exercise. In the muscle samples the active and total amount of the branched-chain 2-oxo acid dehydrogenase complex (BC-complex), the regulatory enzyme in the oxidative pathway of the BCAA, were measured. Glycogen content and activity of mitochondrial marker enzymes were also measured. Blood samples were obtained every 20 min for the measurement of metabolites. Heart rate and rated perceived exertion on the Borg scale were recorded every 10 min. At rest 4.0% +/- 2.5% of the BC complex was active, after 30 min of exercise 9.9% +/- 9.0% and after 120 min 17.5% +/- 8.5% (mean +/- SD). Exercise did not change the total activity. The largest activation was seen in two of the subjects who developed higher blood lactates early on during exercise and decreased their muscle glycogen more (indications of anaerobic metabolism). These data demonstrate that in trained individuals significant increases in the activity of the BC-complex occur only after prolonged intense exercise. In spite of the 4-fold activation, the data support the classical view that amino acids and protein do not contribute substantially as an energy source during exercise, since VO2 increased more than 20-fold.

Patients with McArdle's disease (myophosphorylase deficiency) cannot use muscle glycogen as an energy source during exercise. They therefore are an ideal model to learn about the metabolic adaptations which develop during endurance exercise leading to glycogen depletion. This review summarizes the current knowledge of ammonia and amino acid metabolism in these patients and also adds several new data. During incremental exercise tests in patients with McArdle's disease, forearm venous plasma ammonia concentration rises to a value between 200 and 500 microM. Femoral arteriovenous difference studies show that muscle produces the ammonia. The leg release of both ammonia and glutamine (in mumol/min) has been estimated to be five- to tenfold larger in one of these patients than in healthy individuals exercising at comparable relative work load. Patients with McArdle's disease have a larger uptake of branched-chain amino acids (BCAA) by exercising leg muscles and show a more rapid activation of the muscle branched-chain 2-oxo acid dehydrogenase complex, a key enzyme in the degradation of the BCAA. In general, supplements of BCAA taken before the exercise test lead to a deterioration of exercise performance and a higher increase in heart rate and plasma ammonia during exercise, whereas supplements of branched-chain 2-oxo acids improve exercise performance and lead to a smaller increase in heart rate and plasma ammonia. At constant power output, patients with McArdle's disease show a rapid increase in heart rate and exertion perceived in the exercising muscles, which peak within 10 min after the start of exercise and then fall again ("second wind"). Peak heart rate and peak exertion coincide with a peak in plasma ammonia. Ammonia production during exercise in these patients is estimated to exceed the reported breakdown of ATP to IMP and therefore most likely originates from the metabolism of amino acids. Deamination of amino acids via the reactions of the purine nucleotide cycle and glutamate dehydrogenase are possible pathways. Deamination of glutamine, released by muscle, by glutaminase present in the endothelial cells of the vascular system may also contribute to the ammonia production. The observations made in these patients have led to the hypothesis that excessive acceleration of the metabolism of BCAA drains 2-oxoglutarate in the primary aminotransferase reaction and thus reduces flux in the citric acid cycle and impedes aerobic oxidation of glucose and fatty acids. This draining effect is normally counteracted by the anaplerotic conversion of muscle glycogen to citric acid cycle intermediates, a reaction which is severely hampered in these patients due to the glycogen breakdown defect.(ABSTRACT TRUNCATED AT 400 WORDS)

SUMMARY Percutaneous muscle biopsy is an important and acceptable technique in the study of conditions involving human skeletal muscle. A review of 436 conchotome and needle muscle biopsies obtained over 18 months in this centre is presented.Muscle biopsy is an important tool in the investigation of diseases of muscle, nervous system and connective tissues. The percutaneous techniques have clear advantages over open muscle biopsy, especially regarding the patient's comfort and the absence of unsightly scarring. Despite the small incision, however, specimens can be obtained of suitable size and quality to meet the majority of needs. There is now a large experience of needle muscle biopsy (fig la) in this country.1 2 It is recognised as a simple, rapid and repeatable method of obtaining muscle tissue, safely performed on an outpatient, and applicable to patients of all ages.3 We have recently adopted the technique of percutaneous biopsy using a conchotome4 (fig lb), an instrument primarily intended for nasal surgery, and already in use for muscle biopsy in Scandinavia.58 The conchotome adds further flexibility to investigation of muscle pathology, enabling biopsies to be taken from small muscles unsuitable for needle sampling. Both techniques are in routine use in our unit.In this article we outline our recent experience of percutaneous muscle biopsy, with particular reference to conchotome biopsy of the anterior tibial muscle, and we reinforce the case for percutaneous sampling over open muscle biopsy. PatientsThe age range of the 292 subjects (including 65 children aged 16 years or under) biopsied during the past 18 months was 8