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Biomedical subjects

R G Haller

Publications and source records attributed to R G Haller.

At least 55 records · Page 3Linked to original sources
PubMed1986

Abnormal ventilation during exercise in McArdle's syndrome: modulation by substrate availability.

We evaluated ventilation during cycle exercise in four men lacking myophosphorylase. In submaximal exercise of similar relative intensity, ventilation was higher relative to oxygen uptake in McArdle patients than in normal men. The exercise ventilatory response returned to normal after glucose infusion, by fasting to increase free fatty acid availability or by combining fasting and submaximal exercise. Excessive ventilation in exercise was potentiated by inhibiting lipolysis with nicotinic acid. The excessive ventilatory effort and resultant respiratory alkalosis may contribute to exercise intolerance.

Adolescent↗
PubMed1985

Myophosphorylase deficiency impairs muscle oxidative metabolism.

We studied oxidative metabolism during bicycle exercise in 4 patients with myophosphorylase deficiency. Maximal oxygen uptake (VO2max) was low (14.0 +/- 1.4 ml X kg-1 X min-1, mean +/- SE) compared with that in normal subjects (37.7 +/- 1.9; n = 12) and patients with myalgia (24.9 +/- 1.8; n = 10). Carbohydrate oxidation, as estimated by the respiratory exchange ratio (R), was low relative to workload (max R, mean +/- SE: McArdle's disease, 0.96 +/- 0.02; normal subjects, 1.13 +/- 0.02; myalgia, 1.09 +/- 0.02). Intravenous glucose administration increased maximal oxygen uptake about 20% in those with McArdle's disease, but both VO2max and R remained lower than in control subjects. These findings suggest that the capacity for dynamic exercise in McArdle's disease is limited by the availability of oxidative substrate, and indicate that blood glucose is unable to substitute fully for muscle glycogen as an oxidative fuel. We also found that exercise cardiac output (Q) was excessive relative to oxygen uptake in affected patients (delta Q/delta VO2, mean +/- SE: McArdle's disease, 11.6 +/- 1.7; normal subjects, 4.8 +/- 0.2; myalgia, 5.6 +/- 0.2). This hyperkinetic circulation in exercise may serve to increase the delivery of blood-borne oxidative substrate to working muscle.

Adolescent↗
PubMed1985

Muscle fatigue in McArdle's disease studied by 31P-NMR: effect of glucose infusion.

In muscle phosphorylase deficiency (McArdle's disease) there is an abnormally rapid fatigue during strenuous exercise. Increasing substrate availability to working muscle can improve exercise tolerance but the effect on muscle energy metabolism has not been studied. Using phosphorus-31 nuclear magnetic resonance (31P-NMR) we examined forearm muscle ATP, phosphocreatine (PCr), inorganic phosphate (Pi) and pH in a McArdle patient (MP) and two healthy subjects (HS) at rest and during intermittent maximal effort handgrip contractions under control conditions (CC) and during intravenous glucose infusion (GI). Under CC, MP gripped to impending forearm muscle contracture in 130 s with a marked decline in muscle PCr and a dramatic elevation in Pi. During GI, MP exercised easily for greater than 420 s at higher tensions and with attenuated PCr depletion and Pi accumulation. In HS, muscle PCr and Pi changed more modestly and were not affected by GI. In MP and HS, ATP changed little or not at all with exercise. The results suggest that alterations in the levels of muscle PCr and Pi but not ATP are involved in the muscle fatigue in McArdle's disease and the improved exercise performance during glucose infusion.

Adenosine Triphosphate↗
PubMed1984

Skeletal muscle disease in alcoholism.

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.

Acute Disease↗
PubMed1984

Metabolic control of cardiac output response to exercise in McArdle's disease.

During dynamic exercise cardiac output (Q) normally increases approximately 5 liters per liter of increase in O2 uptake (Vo2) (i.e., delta Q/delta Vo2 approximately equal to 5), indicative of a tight coupling between systemic O2 transport and utilization. We studied four patients with muscle phosphorylase deficiency (McArdle's disease) in whom Q was normal at rest, but delta Q/delta Vo2 was 14.1 +/- 1.3 during bicycle exercise. Procedures designed to alter the availability of substrates were employed to test the hypothesis that the increased delta Q/delta Vo2 is linked to the abnormal metabolic state of skeletal muscle. Fasting plus prolonged moderate exercise was used to increase the availability of plasma free fatty acid (FFA) and resulted in a normalization of delta Q/delta Vo2 (5.3 +/- 0.4). Hyperglycemia (70% above control levels) partially normalized delta Q/delta Vo2. Nicotinic acid lowered plasma FFA concentration and dramatically increased delta Q/delta Vo2 (4.6 to 13.7) when administered after fasting plus prolonged exercise in one patient. Glucose infusion after nicotinic acid administration markedly lowered delta Q/delta Vo2. The results support the hypothesis and suggest that the metabolic state of skeletal muscle, possibly via activation of muscle afferents, participates in the regulation of systemic O2 transport.

Adolescent↗
PubMed1984

Serum and muscle potassium in experimental alcoholic myopathy.

We investigated the possible role of potassium deficiency, a recognized cause of myopathy, in the pathogenesis of experimental acute alcoholic myopathy (EAM) in the rat. Alcohol-treated animals receiving the same dietary potassium as controls developed mild hypokalemia; however, muscle potassium was preserved or elevated even in the presence of scattered muscle fiber necrosis. Increasing dietary potassium raised serum potassium but did not prevent EAM. These data indicate that hypokalemia in EAM is due to potassium redistribution between intra- and extracellular compartments rather than potassium deficiency, and confirm clinical observations that alcohol-induced muscle injury occurs independently of potassium deficiency.

Acute Disease↗
PubMed1984

Pathophysiology of exercise performance in muscle disease.

Diseases of skeletal muscles (myopathies) produce two major patterns of exercise intolerance. In muscular dystrophies, there is a progressive loss of muscle fibers which results in increasing muscle weakness and reduced VO2max due to the loss of functional muscle mass. In disorders of muscle energy metabolism, muscle bulk and resting strength are preserved, but an imbalance in muscle energy production and utilization in exercise results in exertional muscle pain, cramping, weakness, or fatigue. Isometric exercise is impaired by disorders of anaerobic glycolysis. Dynamic exercise is limited by disorders of oxidative metabolism. Maximal oxygen uptake is low in mitochondrial myopathies which affect pyruvate oxidation and electron transport and in glycolytic disorders which limit the availability of carbohydrate for oxidation during high-intensity exercise. In carnitine palmityl transferase deficiency (under non-fasting conditions) VO2max is normal. Excessive cardiopulmonary responses to exercise occur in some mitochondrial myopathies and in myophosphorylase deficiency and may contribute to exercise intolerance in these diseases.

Energy Metabolism↗
PubMed1984

Neuromuscular diseases as models of cardiovascular regulation during exercise.

This article reviews the research performed to date on the cardiovascular responses to exercise in patients with neuromuscular diseases and lesions affecting the transmission of afferent impulses from skeletal muscle. These studies have provided important information about the roles of central command and reflexes from skeletal muscle afferents in circulatory control. Few animal models of neuromuscular diseases are available. Studies of patients with specific defects in skeletal muscle energy metabolism are particularly valuable because the local metabolic state participates in both systemic and local cardiovascular regulation. In patients with certain muscle metabolic defects (e.g., McArdle's disease, carnitine deficiency) cardiac output is normal at rest but increases excessively in relation to oxygen uptake during exercise. The excessive increase in cardiac output during exercise can be totally or partially normalized by increasing the availability of substrate to exercising muscle. These studies provide unique insights into the specific metabolic factors which are involved in cardiovascular regulation.

Afferent Pathways↗
PubMed1983

Low muscle levels of pyridoxine in McArdle's syndrome.

Pyridoxal phosphate is a covalently bound cofactor of glycogen phosphorylase. Phosphorylase is a major muscle protein and therefore represents a significant pool of pyridoxal phosphate. Muscle pyridoxine content was measured in three patients with myophosphorylase deficiency (McArdle's syndrome) in whom there was a marked diminution or absence of phosphorylase protein as determined by acrylamide gel electrophoresis. Total muscle pyridoxine in the patients with McArdle's syndrome (0.55 +/- 0.08 microgram/g wet weight, mean +/- SD) was markedly reduced compared with 11 human control subjects who had normal levels of muscle phosphorylase (total muscle B6 = 2.49 +/- 0.47). Despite such drastically low levels of muscle pyridoxine, these patients had no evidence of pyridoxine "deficiency." These results suggest that low muscle B6 in McArdle's syndrome represents the specific loss of pyridoxal phosphate normally bound to phosphorylase apoenzyme and imply that phosphorylase pyridoxal phosphate accounts for 75 to 80 percent of the total pyridoxine in normal human muscle.

Adolescent↗
PubMed1983

Hyperkinetic circulation during exercise in neuromuscular disease.

Increased oxygen transport by the circulation is normally tightly coupled to increased oxygen uptake (VO2) during exercise; cardiac output (Q) increases 5 to 6 liters for every liter of increased oxygen utilization (delta Q/delta VO2 congruent to 5). We measured cardiac output and oxygen uptake at rest and during bicycle exercise in 7 patients with myalgia without evident muscle disease and 15 patients with myopathies. Resting circulation was normal in all patients, and during exercise the increase in cardiac output relative to oxygen uptake was normal in all myalgia and most myopathy patients. However, in four patients (with dermatomyositis, phosphorylase deficiency, carnitine deficiency, and ocular myopathy with "ragged-red fibers") exercise cardiac output was excessive and delta Q/delta VO2 high, resulting in an abnormally high level of cardiac work for a given level of exercise. This hyperkinetic response may represent aberrant regulation of the circulation by skeletal muscle as a consequence of some myopathies.

Adolescent↗
PubMed1982

Kinetics of carnitine-dependent fatty acid oxidation: implications for human carnitine deficiency.

The relationship between the concentration of carnitine and the oxidation of oleate was examined in homogenates prepared from skeletal muscle, liver, kidney, and heart of the rat, and from canine and human skeletal muscle. the carnitine content of these tissues in situ spanned a wide range, from about 0.1 mumol per gram in rat liver to about 3.0 mumol per gram in human muscle. The concentration of carnitine required for half-maximal rates of fatty acid oxidation in vitro also varied greatly (10 to 15 microM for rat liver to 200 to 400 microM for human muscle), and in rough proportion to the normal carnitine content of the tissues. For any given tissue, the carnitine content seems to be set at a level necessary for optimal rates of fatty acid oxidation. The data provide a plausible explanation for the fact that muscle fatty acid metabolism is severely impaired in the syndrome of human carnitine deficiency, since measured carnitine levels are in the range expected to limit substantially the capacity for fatty acid oxidation.

Animals↗
PubMed1980

Alcoholic rhabdomyolysis: an experimental model in the rat.

The main features of alcoholic rhabdomyolysis-skeletal muscle necrosis, marked elevation of serum creatine phosphokinase, and myoglobinuria-were produced in rats by a combination of relatively prolonged (2 to 4 weeks) exposure to ethanol and a brief period of food deprivation. This observation suggests that fasting may similarly trigger muscle injury during binge drinking in man. The effect of fasting is in part related to an increase in blood alcohol due to reduced alcohol clearance and in part caused by a fasting-induced potentiation of the toxic effects of high concentrations of alcohol of skeletal muscle.

Alcoholism↗
PubMed1976

Avoidance behavior and ileum motility post-cingulumotomy in monkey.

Two experiments were conducted utilizing rhesus monkeys to determine (i) the effects of cingulumotomy on conditioned-avoidance acquisition and extinction and (ii) the effects of avoidance learning on distal ileum motility in control- and cingulum-lesioned animals. Active (AAR) and passive (PAR) avoidance schedules singly or in combination were employed during short daily periods (less than 2 hr) of "shaping," training, acquisition, and extinction. The data indicated that the control-lesion and cingulum groups did not differ in the acquisition or extinction of an AAR. The cingulum group, however, showed a significant deficit in the acquisition of a PAR and a noticeably slower rate of lever pulling during avoidance trials in the combined avoidance training sessions. The results also suggested that ileum motility and avoidance behavior parallel on another, i.e., if either changed the other often changed in the same direction; that cingulum monkeys seemed to be less "reactive" than control-lesion monkeys; and that cingulum animals may been somewhat more regular in their percent daily motility patterns than the control animals.

Animals↗
PubMedDate not supplied

Effect of perfusion on exercised muscle: MR imaging evaluation.

An ischemic clamp model of exercise was used to evaluate the potential role of blood flow in mediating changes in the magnetic resonance imaging appearance of skeletal muscle. Proton relaxation times of muscle were serially estimated in 10 healthy subjects (a) before exercise, (b) after exercise in the presence of vascular occlusion (VO1), (c) during vascular reocclusion after 1 minute of reperfusion (VO2), and (d) after reinstitution of continuous flow. T1 and T2 of active muscles were increased during VO1. During VO2, there were additional increases in relaxation times of active muscles. Reinstitution of continuous flow was associated with a continuous decrease in the T2 of exercised muscle. Hence, blood flow was not required for increases in T1 and T2 with exercise. Additional relaxation time increases occurred after a brief period of reperfusion; however, continuous flow was associated with a decrease in T2.

Adult↗
PubMedDate not supplied

Experimental acute alcoholic myopathy--a histochemical study.

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.

Alcoholism↗