Dietary and serum lipids in individuals with spinal cord injury living in the community.

A cross-sectional study of 189 community-dwelling persons with spinal cord injury (SCI) (a) assessed levels of dietary and serum lipids, (b) determined the proportion of persons whose levels were out of the recommended/desired range, and (c) identified predictors of dietary and serum lipids. Lipid levels were out of range for a substantial proportion of the sample. Older persons were likely to have higher serum cholesterol and higher triglyceride levels than younger persons. Men tended to have higher intake of dietary cholesterol and lower levels of HDL than women. Caucasians and Hispanic-Americans tended to have higher triglycerides than African-Americans. Persons who had lived with SCI less time tended to have higher saturated fat intake and higher triglycerides than those who had lived with it longer. Greater saturated fat intake was associated with higher serum cholesterol after controlling for age. Studies are needed that test the effectiveness of various interventions on controlling dietary and serum lipids for persons with SCI.

Factors which influence alterations of phosphates and pH in exercising human skeletal muscle: measurement error, reproducibility, and effects of fasting, carbohydrate loading, and metabolic acidosis.

Previous studies have shown considerable variability in the metabolic response of human skeletal muscle during a standardized exercise protocol. The goal of these studies was to investigate the factors responsible for the broad range of metabolic changes produced by fatiguing exercise. Experiments were performed to quantitate the measurement error of 31P nuclear magnetic resonance spectroscopy of human muscle, the reproducibility of changes within a single subject, and the effects of fasting, carbohydrate loading, and metabolic acidosis. The results show that none of these factors appear to be responsible for the wide variation between subjects. However, the effects of training and genetic factors were not investigated and are likely to be responsible for the substantial variability between subjects.

Phosphorylation of vertebrate nonmuscle and smooth muscle myosin heavy chains and light chains.

In this article we review the various amino acids present in vertebrate nonmuscle and smooth muscle myosin that can undergo phosphorylation. The sites for phosphorylation in the 20 kD myosin light chain include serine-19 and threonine-18 which are substrates for myosin light chain kinase and serine-1 and/or -2 and threonine-9 which are substrates for protein kinase C. The sites in vertebrate smooth muscle and nonmuscle myosin heavy chains that can be phosphorylated by protein kinase C and casein kinase II are also summarized. Original data indicating that treatment of human T-lymphocytes (Jurkat cell line) with phorbol 12-myristate 13-acetate results in phosphorylation of both the 20 kD myosin light chain as well as the 200 kD myosin heavy chain is presented. We identified the amino acids phosphorylated in the human T-lymphocytes myosin light chains as serine-1 or serine-2 and in the myosin heavy chains as serine-1917 by 1-dimensional isoelectric focusing of tryptic phosphopeptides. Untreated T-lymphocytes contain phosphate in the serine-19 residue of the myosin light chain, and in a residue tentatively identified as serine-1944 in the myosin heavy chain.

The fatigue of rapid repetitive movements.

Normal subjects (n = 7) performed rapid voluntary isometric contractions of the adductor pollicis and the tibialis anterior. Within the first minute of this low-intensity exercise, the speed of tension development slowed, accompanied by a prolongation in EMG burst duration. In contrast, electrically evoked contractions either became more rapid (twitch) or did not change (tetanus), suggesting a fatigue of central origin. 31P NMR measurements of high-energy phosphates showed that the relationship between the fall of maximum force and changes of phosphates and pH was similar to that produced by other high-intensity fatiguing exercise protocols. Thus, rapid movements produce fatigue through two major mechanisms. First, there is slowing of the speed of tension development which appears secondary to central fatigue. Second, the decline of muscle force is primarily attributable to changes in muscle pH or inorganic phosphate, which usually occurs only after high-intensity (but non-rapid) exercise.

Dantrolene sodium and fatigue of long duration.

A long-lasting impairment of muscular force generation follows fatiguing exercise (fatigue of long duration), the physiological basis of which is not well understood. To investigate the role of reduced calcium release in long-lasting fatigue, we examined the effects of dantrolene sodium, which selectively decreases calcium release from the sarcoplasmic reticulum. The drug impaired muscle function in a pattern identical to that of long-lasting fatigue. The results are consistent with either independent effects of dantrolene and exercise at the same site in the excitation-contraction coupling chain, or independent actions at separate serial sites.

Fatigue and myalgia in AIDS patients.

Fatigue and myalgia are common in patients with acquired immunodeficiency syndrome (AIDS). To determine whether altered muscle metabolism or impaired activation of muscle might account for these symptoms, we utilized three different exercise protocols to produce fatigue in nine AIDS patients who complained of both fatigue and exercise-exacerbated myalgia. Five were taking azidothymidine (AZT), which may cause a mitochondrial myopathy. Simultaneous measures of force, EMG, and muscle metabolites (phosphocreatine, inorganic phosphate, adenosine triphosphate, and intracellular pH) using phosphorus nuclear magnetic resonance spectroscopy were performed during fatigue and recovery. There were no significant differences between patients and controls in terms of fatigability, muscle metabolism, or muscle activation. These results provide no support for the hypothesis that fatigue or myalgia in AIDS patients derives from altered muscle metabolism or that AZT produces mitochondrial myopathy.

Constant relationships between force, phosphate concentration, and pH in muscles with differential fatigability.

We examined the relationships between muscle force and both phosphate and hydrogen ion concentrations in muscles with differential fatigability and in different types of exercise. We measured force and 31phosphorus nuclear magnetic resonance spectra from the tibialis anterior (a slow-contracting, fatigue resistant, postural leg muscle) during a sustained maximum contraction (anaerobic exercise) and during intermittent contractions (aerobic exercise). We observed similar relationships between the decline in muscle force during fatigue and changes in both phosphate and hydrogen ion concentrations during both aerobic and anaerobic exercise in tibialis anterior. Furthermore, these relationships were similar to those previously observed in the adductor pollicis. The demonstration of constant relationships between muscle contraction force and metabolism under different exercise conditions and in muscles of different function supports the view that both phosphate and hydrogen ions are important regulatory factors in the fatigue of human muscle.

Excessive muscular fatigue in patients with spastic paraparesis.

We used intermittent tetanic contractions and 31P magnetic resonance spectroscopy to investigate human tibialis anterior muscle metabolism and fatigability in a group of patients with spastic paraparesis and in normal controls. During intermittent tetanic stimulation, the decline in tension was significantly greater in patients than in controls, and the half-relaxation time of the tetanus was more prolonged. Moreover, the decline in phosphocreatine and intracellular pH was significantly greater in patients than in controls. These observations suggest that biochemical changes in the muscles of patients with upper motor neuron lesions may contribute to their excessive fatigability.

Neonatal hyperthyroidism enhances growth of the heart but not of skeletal muscle.

Comparison of growth and biochemical development of the heart and skeletal muscle (gastrocnemius) in normal rats and those treated with triiodothyronine (T3) (0.1 micrograms/g bw, s.c.) daily, from birth until weaning (day 25), revealed that hyperthyroidism selectively enhanced cardiac growth as shown by marked increases in total content (per heart) of DNA (25%), RNA (22%), protein (31%), and myofibrillar protein (30%), as well as the activity of myosin ATPase (11-20%). On the contrary, the above parameters were significantly decreased in the skeletal muscle of hyperthyroid rats as was body weight. Termination of T3 treatment on day 25 led to resumption of rapid body growth which was not complete even by day 90. Cardiac growth decelerated in rehabilitating rats, however, resulting in final reduction of all growth parameters, except DNA content which was equal in 90-day control and rehabilitated animals. Muscle growth in terms of DNA and RNA content failed to respond to rehabilitation and continued to be lower than control animals while protein synthesis was relatively enhanced. It is concluded that neonatal hyperthyroidism markedly enhanced growth of the heart but not of skeletal muscle. This condition not only inhibited growth of the muscle during the T3 treatment period but also led to permanently reduced DNA content and other growth parameters even two months after discontinuation of treatment.

The metabolic basis of recovery after fatiguing exercise of human muscle.

We investigated the metabolic basis of human muscular fatigue and recovery utilizing 31P magnetic resonance spectroscopy and measurements of maximum voluntary contraction (MVC). We produced fatigue by sustained MVC for 4 minutes in 2 different muscles (adductor pollicis, tibialis anterior) and obtained similar results in both muscles. During fatiguing exercise, there was a nonlinear relationship between MVC and both phosphocreatine and total inorganic phosphate. By contrast, there was a roughly linear relationship between the decline in MVC and the accumulation of both H+ and H2PO4-. However, during recovery after exercise, MVC rapidly returned to control levels while H+ recovered with a much slower time course. On the other hand, H2PO4- rapidly returned to control values with a time course similar to MVC. In addition, the relationship of H2PO4- to MVC was similar during both fatigue and recovery. Thus, during fatigue as well as during recovery, changes in MVC correlate best with H2PO4-, suggesting that this metabolite is an important factor in human muscle fatigue.

Nonmetabolic fatigue in exercising human muscle.

Human muscle fatigue, assessed by declining maximum voluntary contraction (MVC), may be caused by impairment of excitation-contraction coupling as well as by metabolic alterations within the muscle. To distinguish between these 2 possibilities, we assessed changes in excitation-contraction coupling by measuring twitch tension (TT) and twitch potentiation (P-TT) of the human adductor pollicis and tibialis anterior, while we analyzed metabolic changes using 31P magnetic resonance spectroscopy. Low-intensity exercise produced a much greater fall of TT and P-TT than MVC, high energy phosphates, or intracellular pH (pHi). In addition, the recovery of TT and P-TT was much slower than recovery of MVC, high energy phosphates, or pHi. These results suggest that the greater fall of TT and the delayed recovery following low-intensity exercise are caused by impaired excitation-contraction coupling.

Early responses of skeletal muscle in recovery from hypothyroidism.

Postnatal growth of skeletal muscle (m. gastrocnemius) was compared in rats under euthyroid, hypothyroid and hypothyroid-rehabilitated conditions. In normal (euthyroid) animals, gastrocnemius muscle grows significantly in terms of weight (150 x) from birth to the young adult and, in terms of total contractile myofibril protein (15 x) and myosin ATPase activity (10 x) between days 25 and 90. Rats made hypothyroid (with 0.1% w/v propylthiouracil, PTU) from birth show reduced growth. At 25 days (weaning), compared with euthyroid, muscle weight is only 25% of normal, and a similar reduction is found in total DNA, RNA, protein, myofibril protein, and myosin ATPase activity. These deficits, already significant by day 10, are more marked by day 50 due to the near arrest of growth. Hypothyroid rats allowed to recover by PTU withdrawal after day 25 (rehabilitated) undergo marked compensatory muscle growth. By day 90, muscle weight and protein content increase 50 x, DNA 7 x and RNA 17 x. Over this period, total myofibrillar protein and myosin ATPase increase 20-40 x, but are still below those of 90-day controls, suggesting that the severe growth retardation had not yet been fully compensated. Early thyroid deficiency drastically reduces the normal age-related growth of skeletal muscle and severely retards the development of contractile elements, affecting muscle hypertrophy (protein content) more than cell proliferation (DNA content). Rehabilitation compensates to a major degree for this growth retardation. These results underline the key role of thyroid hormones in regulating development and maturation of skeletal muscle throughout the preweaning and postweaning phases of growth.

31P nuclear magnetic resonance studies of high energy phosphates and pH in human muscle fatigue. Comparison of aerobic and anaerobic exercise.

The goal of these experiments was to investigate the relationship of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), monobasic phosphate (H2PO4-), and pH to human muscle fatigue. Phosphates and pH were measured in adductor pollicis using 31P nuclear magnetic resonance at 2.0 Tesla. The force of muscle contraction was simultaneously measured with a force transducer. The effects of aerobic and anaerobic exercise were compared using two exercise protocols: 4 min sustained maximal voluntary contraction (MVC) and 40 min of repeated intermittent contractions (75% MVC). The sustained maximal contraction produced a rapid decline of MVC and PCr, and was accompanied by a rapid rise of Pi, H+, and H2PO4-. Intermittent exercise produced steady state changes of MVC, pH, and phosphates. No significant changes of ATP were found in either protocol. During fatiguing exercise, PCr and Pi had a nonlinear relationship with MVC. H+ showed a more linear correlation, while H2PO4- showed the best correlation with MVC. Furthermore, the correlations between MVC and H2PO4- were similar in sustained (r = 0.70) and intermittent (r = 0.73) exercise. The highly significant linear relationship between increases of H+ and H2PO4- and the decline of MVC strongly suggests that both H+ and H2PO4- are important determinants of human muscle fatigue.

Compensatory cell proliferation and growth in the rat heart after postnatal hypothyroidism.

Measurement of total DNA, RNA, and protein as well as weight of the heart in male rats at 10, 25, 50, and 90 postnatal days revealed that hypothyroidism, as induced by administration from birth of the goitrogen propylthiouracil (PTU), results in highly significant reductions in cardiac cell proliferation and cell growth. These inhibitory effects on hyperplastic and hypertrophic growths were less drastic during the suckling period than during the postweaning period. In the latter period, heart growth of the hypothyroid animals was found to remain at a standstill with regard to all the parameters measured. When, after 25 days of hypothyroidism, PTU treatment was discontinued, the retarded heart showed marked signs of rehabilitation and compensatory development. Indeed, by day 90, total DNA content had essentially compensated for its deficit but total RNA, protein content, and weight, though showing marked compensatory surges (from 80-90% deficit to 20-30%), were not yet fully compensated. The results clearly indicate that the growing heart has a marked ability to be rehabilitated from severe hypothyroid retardation, showing within 2 mo full compensation of cell number and nearly complete compensation of cell growth. It is suggested that rehabilitation of the heart is brought about by physiological restoration not only of the thyroid hormones but also of growth hormone and possibly other thyroid-dependent growth factors.