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Biomedical subjects

J J Heffron

Publications and source records attributed to J J Heffron.

At least 19 recordsLinked to original sources

Skeletal muscle sarcoplasmic reticulum in porcine malignant hyperthermia.

To examine the function of sarcoplasmic reticulum (SR) in malignant hyperthermia, SR was isolated from semitendinosus muscle of normal and genetically susceptible Poland China swine. Determinations included rate of calcium binding (oxalate absent), rate and capacity of calcium uptake (oxalate present), and spontaneous calcium release (in the absence of ionic depolarization or calcium) with and without halothane, using the millipore filtration technique. Rate of calcium binding, and rate and capacity of calcium uptake were decreased, and spontaneous calcium release was greater in SR fragments from susceptible swine as compared to those from normal swine. Halothane 0.5% slightly increased the rate of calcium binding in susceptible and normal SR. Above 1%, halothane decreased calcium binding rate, and uptake rate and capacity, and increased calcium release similarly in susceptible and normal SR. These differences in SR function were insufficient to explain the etiology of malignant hyperthemia, nor did the effect of halothane account for its triggering action.

Animals

Fine structure of the homologous tergo-coxal muscles of flying and flightless beetles.

The flight-related tergo-coxal muscles of flying and flightless beetles are compared. In the flying beetle, Pachynoda sinuata, the myofibrils and cylindrical and the myofilaments packed in double hexagonal arrays. The sarcomeres are short (2.8 micrometer) and wide with many large, closely packed adjacent mitochondria but the sarcoplasmic reticulum is poorly developed in this fibrillar (asynchronous) muscle. Sarcoplasmic glycogen in rosette form is abundant. In the flightless beetle, Anthia thoracica, the myofibrils are lamellar-like with sarcomeres of 5.3 micrometer. The myosin filaments form a single hexagonal array each thick filament having an orbital of 11 to 12 thin filaments. The width of the Z-line (120 nm) of A. thoracia muscle was twice that of the Z-line of P. sinuata muscle. The sarcoplasmic reticulum and T-system are well-developed in this afibrillar (synchronous) muscle. Few glycogen granules are present. Triangular projections of the sarcolemma occur regularly opposite the Z-lines in A. thoracica and they appear to extend into the Z-lines. Membranous connections joint adjacent Z-lines in A. thoracica and occasionally in P. sinuata.

Animals

Porcine malignant hyperthermia: role of skeletal muscle in increased oxygen consumption.

During malignant hyperthermia (MH) induced by halothane and succinylcholine, oxygen consumption (VO2) of whole body, muscle and the splanchnic area was calculated from measurements of blood flow and arteriovenous oxygen content difference. Caudal body blood flow was isolated and measured (six animals) for determination of average muscle VO2 in the hind limbs, buttocks, and flanks. The increase in muscle VO2 was extrapolated to total skeletal muscle and compared with the increase in whole body VO2 (same six animals). The average increase in VO2 for both total muscle and whole body during the period of maximum increase was about 6 ml O2/min/kg body weight. Splanchnic VO2 (four animals) tended to decrease during MH. The data support the hypothesis that the metabolic changes in MH are due to a disorder of skeletal muscle and that the increase in whole body VO2 is due to the increase in muscle VO2.

Animals

Oxygen uptake of canine whole body and hind limb with hypocapnic alkalosis.

The effect of hypocapnic alkalosis induced by hyperventilation on whole-body and hind-limb oxygen uptake (VO2) was studied in dogs anesthetized with pentobarbital. In the intact dog with a self-perfused hind limb, increasing pHa from 7.41 to 7.58 increased whole-body VO2 8% and decreased hind-limb VO2 6%. Isolated hind limbs perfused with heparinized whole blood had similar decreases in VO2 with increases in arterial blood pH (pHa). However, isolated hind limbs perfused with whole blood containing citrate, phosphate, and dextrose (CPD) showed muscle twitches, had larger VO2 values at identical pHa's, and had an increase in VO2 with increase in pHa. These changes with a CPD perfusate were associated with low levels of ionized calcium (less than 0.5 mEq/1), disappeared when calcium ion spontaneously increased to 1.0 mEq/1, and could be prevented or abolished by the addition of calcium chloride, dantrolene, d-tubocurarine, or succinylcholine. These results are in accord with the findings of others regarding an increase in whole-body VO2 with hypocapnic alkalosis, but do not support a contributory role of skeletal muscle to the overall increase.

Alkalosis

Malignant hyperthermia syndrome--evidence for denervation changes in human skeletal muscle.

The presence of denervation-like changes and abnormal mitochondria in the muscle of carriers of the malignant hyperthermia syndrome suggest a neuropathic basis for the human syndrome. A defect in mitochondrial ATP synthesis resulting from denervation, and potentiated by some general anaesthetics, may be the primary muscle fibre lesion in the human malignant hyperthermic syndrome.

Adenosine Triphosphatases

Observations on plasma creatine phosphokinase activity in dogs.

Plasma creatine phosphokinase (PCPK) activity was determined in 14 clinically normal adult pedigree dogs of various breeds with an activated enzyme assay medium. PCPK levels were not significantly influenced by the time of sampling, body mass or eating, but there was a significant correlation (P is less than 0.05) between PCPK levels and moderate physical activity. The mean enzyme activity was 22.9 iu/litre at 30 degrees C. The PCPK levels are 10 times greater than those obtained by other authors with the non-activated enzyme assay method.

Animals

Weakness associated with the pathological presence of lipid in skeletal muscle: a detailed study of a patient with carnitine deficiencey.

A patient with muscular weakness demonstrating pathological lipid accumulation and abnormal mitochondria in skeletal muscle has been studied. The lipid accumulation and mitochondrial changes are thought to be related to the established deficiency of carnitine in this patient's muscle. The symptoms of muscular weakness associated with lipid accumulation in the skeletal muscle in the absence of complaint of muscle cramps or myglobinuria are thought to be diagnostic of carnitine deficiency. The failure of the sarcoplasmic reticulum to accumulate Ca2+ is discussed. The patient's strength responded dramatically when propranolol was added to his steroid therapy.

Adult

Inhibition of actomyosin ATPase by high concentrations of 5-hydroxytryptamine. Possible basis of lesion in 5HT-induced experimental myopathy.

The effect of 5-hydroxytryptamine (5HT) on the ATPase activity and sulphydryl group reactivity of mammalian skeletal muscle actomyosin has been studied. 5HT inhibited the Mg2+-activated but not the Ca2+-activated ATPase activity of actomyosin. It slightly activated myosin ATPase. The sulphydryl groups of actomyosin reacting with 5,5'-dithiobis-(2-nitrobenzoic acid) were blocked by concentrations of 5HT which inhibited the Mg2+-activated ATPase. The significance of the results are discussed in relation to the muscle lesions in the experimental myopathy induced by 5HT and imipramine.

Actomyosin

'Picture frame' fibres in a carrier of the trait for malignant hyperpyrexia.

A member of a family which was known to be susceptible to malignant hyperpyrexia, who was identified as a carrier by the presence of an elevated serum creatine-phosphokinase, has been investigated further. Muscle was examined biochemically, and the study included the sarcoplasmic ATPase-activity, actinomycin, Mg2+ ATPase activity, ATP, phosphocreatine and glucose-6-phosphate. In addition, the calcium uptake by the sarcoplasmic reticulum was studied. The histochemical analysis of the muscle revealed the presence of a new fibre type characterised by a dense rim of ATPase activity, which gives the impression of a 'picture-frame'. Ultramicroscopic study revealed changes in the mitochondria and areas of myofibrillar disruption with swelling of the sarcoplasmic reticulum.

Adenosine Triphosphatases

Xanthine, hypoxanthine and muscle pain. Histochemical and biochemical observations.

A suspected case of xanthine oxidase deficiency has been further investigated. The patient complained of arthralgia and myalgia. Further studies included histochemical and ultramicroscopic analysis of muscle sarcoplasmic reticulum, and biochemical studies. High levels of xanthine and hypoxanthine were found, while uric acid was absent in the muscle extracts.

Adenosine Triphosphatases