Biomedical subjects

E M Gallant

Publications and source records attributed to E M Gallant.

42 records · Page 3Linked to original sources

PubMed1983

Malignant hyperthermia: responses of skeletal muscles to general anesthetics.

Anesthetic-induced malignant hyperthermia (MH) originally attracted scientific interest because of the associated high fatality rate. Recently, the introduction of treatment with the muscle relaxant dantrolene sodium has dramatically reduced the frequency of death from MH. Nonetheless, diagnosing MH susceptibility remains a problem because it necessitates a muscle biopsy specimen that must be tested in a specially equipped laboratory. Thus, diagnosis is both expensive and invasive. Development of simpler and less invasive methods would be aided by identification of the primary defect underlying initiation of MH. Our understanding of whole-body responses during MH episodes and the development of treatment with dantrolene sodium have both resulted from studies of porcine MH, which is similar to the syndrome in humans. Investigations of porcine MH have demonstrated that the defect responsible for initiation of MH must be located in skeletal muscle. Many abnormal responses of MH muscle have been identified after exposure to triggering agents. These defects contribute to the maintenance and amplification of the MH episode once it has been initiated. The primary defect responsible for triggering this complex chain of events, however, has thus far eluded definition.

Animals↗

PubMed1982

Cellular membrane potentials and contractile threshold in mammalian skeletal muscle susceptible to malignant hyperthermia.

An increase in external K+ can generate contractile force in muscle, and K+ contractures are an established means to determine the effect of an agent on the relation between membrane potential and mechanical activity [8]. We have used K+-contractures to further test our hypothesis [5] that abnormal cell membrane potential responses are intrinsic to skeletal muscle of Poland China pigs susceptible to malignant hyperthermia (MHS), and a nervous system is not required to initiate malignant hyperthermia (MH). Recently it has been shown that K+-induced contractures in certain skeletal and cardiac muscles might not be determined only by cellular membrane potential changes predicted by the tendency for K+ to move in accord with its electrical and concentration gradients [3, 12]. We report here that normal and diseased skeletal muscles respond differently to raised external K+, which supports the idea that the onset of the MH syndrome is determined by a defect associated with a site in muscle cells superficial to the cytoplasm rather than, as has been suggested, within the cell or in the nervous system [7]. In addition, we find that porcine skeletal muscles, like certain other muscles, produce much less force in K+ than expected from our measurements of the relationship between membrane potential and external K+.

Animals↗

PubMed1980

Histochemical observations on muscle from normal and malignant hyperthermia-susceptible swine.

A comparison was made of muscle from two locations in both the longissimus and the semitendinous muscles of normal and malignant hyperthermia-susceptible swine. Serial frozen sections were stained for alkali-stable adenosine triphosphatase (ATPase), phosphorylase, and the oxidative enzymes succinate dehydrogenase and reduced nicotinamide adenine dinucleotide (NADH)-diaphorase. Myofiber types were identified on the basis of these staining reactions. There was no consistent statistically significant difference between muscle from normal and muscle from susceptible swine with any system of fiber classification. This is contrary to several published reports but consistent with physiologic studies which indicate that both oxidative and glycolytic pathways are abnormally active during the onset of malignant hyperthermia.

Adenosine Triphosphatases↗

PubMed1980

Mechanical properties of normal and malignant hyperthemia susceptible porcine muscle: effects of halothane and other drugs.

Malignant hyperthemia, which can be initiated in susceptible humans and swine by the volatile anesthetic halothane, appears to result from abnormal responses in skeletal muscle. We have inferred the primary defect in susceptible muscles by observing their responses to certain drugs. Furthermore, we compared the responses of cut muscle cell preparations, such as those used in the diagnostic caffeine test, with those of intact muscle cells. Specifically, we investigated the effects of halothane, caffeine, succinylcholine and catecholamines on the mechanical properties of intact muscle cells from normal pigs, mice and frogs and susceptible pigs. The results from intact and paired cut cell preparations were qualitatively similar. Halothane (2%) caused a 30% decrease in peak tetanic tension in susceptible porcine muscle but less than a 10% change in other muscles. Halothane potentiated twitch tension in frog and susceptible pig muscle. The latter was 4 times more sensitive to caffeine twitch potentiation than normal muscle. Porcine intercostal muscles were more sensitive to caffeine than limb extensor muscles and the difference between normal and susceptible muscle was less with intercostal muscles. Succinylcholine and catecholamines had small and opposite effects on porcine muscles; when used together in combination with halothane there was little effect on normal muscle but a dramatic decrease in tetanic tension and rapid onset of contracture in susceptible muscle.

Animals↗

PubMed1979

Porcine skeletal muscle for physiological studies.

The common digital extensor (lateral head) is one of the few porcine muscles of convenient dimensions for in vitro studies of intact cells. Its removal and use in physiological studies are described.

Animals↗

PubMedDate not supplied

Role of plasma membrane defect of skeletal muscle in malignant hyperthermia.

Halothane, at clinical concentrations, depolarizes the plasma membrane of skeletal muscle from Poland China pigs susceptible to malignant hyperthermia but does not affect the resting membrane potential of muscle from normal poland China pigs, mice, or frogs. The depolarization is reduced or partially reversed in the presence of dantrolene sodium. We suggest the possibility that malignant hyperthermia may be initiated by this abnormal depolarization of skeletal muscle by halothane.

Animals↗