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Biomedical subjects

J J Heffron

Publications and source records attributed to J J Heffron.

At least 55 records · Page 3Linked to original sources
PubMed1981

Stimulation of calcium-ion efflux from liver mitochondria by sodium ions and its response to ADP and energy state.

The Ruthenium Red-insensitive efflux of Ca2+ from previously loaded rat liver mitochondria was studied as a function of the added Na+ concentration and ADP present. Stimulation of Ca2+ efflux is sigmoidally dependent on the Na+ concentration; maximal stimulation of efflux was observed with 12--15 mM-NaCl. Na+-stimulated Ca2+ efflux from liver mitochondria is about one-tenth that from cardiac mitochondria. No synergistic effect of K+ on the Na+-stimulated efflux was found. The alkali-metal cations other than Na+ did not stimulate efflux and did not prevent stimulation by Na+. In the absence of Na+, Ca2+ efflux was diminished by added ADP, but the Na+-stimulated efflux was made correspondingly greater as ADP concentration was increased to 16 microM. The Na+-stimulated Ca2+ efflux was inhibited by 70% by oligomycin and was not observed in the presence of antimycin. It is suggested that failure to observe Na+-stimulation of Ca2+ efflux from liver mitochondria by some investigators is attributable to a high basal efflux existing before addition of the Na+ salt.

Adenosine Diphosphate↗
PubMed1981

Influence of pH, temperature, halothane and its metabolites on osmotic fragility of erythrocytes of malignant hyperthermia-susceptible and resistant pigs.

Erythrocyte fragility of malignant hyperthermia-susceptible and resistant pigs has been examined as a function of pH and temperature in the absence and presence of halothane and its metabolites. A decrease in pH from 7.40 to 6.95 increased the fragility of both susceptible and resistant pigs, but the increase in susceptible animals was significantly greater than that in resistant animals. An increase in temperature led to a reduction of erythrocyte fragility of both types of pig. The most consistent differences in haemolysis between susceptible and resistant pigs occurred at sodium chloride concentrations of 0.120 and 0.137 mol litre-1. At all pH values examined and at 39 and 41 degrees C, but not at 43 degrees C, erythrocytes from susceptible pigs showed greater haemolysis in sodium chloride 0.120 and 0.137 mol litre-1 than did erythrocytes from resistant pigs. Halothane or its metabolites, at concentrations occurring during anaesthesia, did not alter erythrocyte fragility.

Animals↗
PubMed1981

Plasma cortisol levels in pigs susceptible and resistant to malignant hyperthermia.

Plasma cortisol levels were measured in Landrace pigs susceptible to malignant hyperthermia (MH), Landrace pigs resistant to MH and in Largewhite pigs, during growth halothane anaesthesia and after injections of Synachten. From 3 to 6 months of age mean cortisol levels in susceptible Landrace were 193,2 +/- 49,7 nmol/l, in resistant Landrace 220,8 +/- 24,8 nmol/l and in Largewhite 278,8 +/- 13,8 nmol/l. These values were not significantly different. After injection of 1 mg Synachten intravenously, plasma cortisol levels did not increase significantly in susceptible pigs. In resistant landrace pigs and Largewhite pigs the plasma levels after injection were significantly greater than pre-injection levels (P less than 0,05) and significantly different from susceptible Landrace levels. During halothane anaesthesia, cortisol levels rose more in resistant pigs than in susceptible pigs, but differences were no significant. These results suggest that susceptible pigs have a decreased ability to secrete cortisol during stress.

Adrenocorticotropic Hormone↗
PubMed1980

Effects of temperature, adenosine triphosphate and magnesium concentrations on the contraction of actomyosin isolated from halothane-sensitive and -insensitive German Landrace pigs.

The effects of temperature, adenosine triphosphate and magnesium on the calcium sensitivity of actomyosin were investigated on actomyosin obtained from six halothane-sensitive and five halothane-resistant German Landrace pigs. No difference in the contractile properties was found in actomyosin from the two types of pig. However, in both types calcium sensitivity of the actomyosin was lost at temperatures slightly greater than those occurring physiologically. Both ATP and Mg2+ protect against the loss of calcium sensitivity. These results suggest that the basic lesion in halothane-induced malignant hyperthermia does not lie in the contractile proteins. It is likely, however, that the decreases in intracellular ATP and Mg2+ concentrations which occur in pigs during malignant hyperthermia, contribute to the development of the syndrome.

Actomyosin↗
PubMed1980

A halothane-induced biochemical defect in muscle of normal and malignant hyperthermia-susceptible Landrace pigs.

Muscle adenosine triphosphate (ATP), glucose-6-phosphate, phosphocreatine, and pH were measured in nine malignant hyperthermia (MH)-susceptible and 14 MH-resistant Landrace pigs. Muscle biopsies were taken before (under barbiturate anesthesia) and after exposure to halothane. When compared to levels during barbiturate anesthesia, exposure to halothane had no immediate effect on muscle ATP levels in either MH-susceptible or -resistant pigs. However, once malignant hyperthermia developed in susceptibe pigs ATP levels decreased significantly. In both susceptible and resistant pigs halothane increased muscle glucose-6-phosphate and decreased muscle phosphocreatine and pH significantly below control levels observed during barbiturate anesthesia. In susceptible pigs these changes were significantly more marked than were the changes produced in resistant pigs. These data indicate that the effect of halothane on muscle metabolism is similar in both MH-resistant and -susceptible pigs. The results suggest that the effect of halothane is to inhibit aerobic metabolism by preventing mitochondrial dehydrogenation of pyruvate. Inhibition is complete in susceptible pigs but only retarded in resistant pigs. In susceptible pigs the consequent lactacidosis, hyperthermia, and reduction in ATP synthesis contribute to the development and maintenance of rigidity.

Adenosine Triphosphate↗
PubMed1979

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↗
PubMed1978

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↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1976

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↗
PubMed1976

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↗