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Biomedical subjects

E H Flewellen

Publications and source records attributed to E H Flewellen.

At least 19 recordsLinked to original sources
PubMed1987

Calcium and magnesium content of skeletal muscle. Studies in subjects undergoing diagnostic testing for malignant hyperthermia.

Ca2+ and Mg2+ contents were measured and compared among three different malignant hyperthermia susceptible (MHS) diagnostic groups. No difference was found among mean values for Ca2+ content, whereas Mg2+ content was greater in MHS muscle. Variance of measured values was unequal and greatest among MHS muscles, suggesting a possible abnormal distribution associated with MHS. Although more muscle fibres with Ca2+ less than or equal to 12 mumol g-1 were observed in MHS muscle, this difference was not statistically significant. In contrast, non-parametric analysis showed that the population of Mg2+ values was significantly greater in the MHS muscle. This study suggests that the distribution of Ca2+ and Mg2+ values is different in MHS muscle as a result of unknown genetic factors associated with the disease.

Calcium↗
PubMed1987

Comparison of Ca++ uptake and spontaneous Ca++ release from sarcoplasmic reticulum vesicles isolated from muscle of malignant hyperthermia diagnostic patients.

Inward Ca++ transport and spontaneous Ca++ release activities were compared among sarcoplasmic reticulum (SR) membrane fractions isolated from human skeletal muscle in patients undergoing malignant hyperthermia (MH) diagnostic contracture testing. Two different membrane fractions were isolated, a heavy (8-12,000 X g) and light (12-48,000 X g) fraction, from each diagnostic subject. The rates of inward Ca++ transport were faster in light SR compared to heavy SR, but no statistically significant difference was observed among MH diagnostic groups. Spontaneous Ca++ release occurred at optimum Ca++ preload in all SR fractions and this preload did not differ among MH diagnostic groups. Optimal Ca++ preload for rate of spontaneously released Ca++ was greater in light SR compared to heavy SR. Similarly, rate of Ca++ release was faster in light SR than in heavy SR, but no difference in rate of spontaneously released Ca++ was observed among MH diagnostic groups. Amount of Ca++ released did not differ among SR fractions and it did not differ among diagnostic groups. In contrast to previous studies showing a defect in Ca++-induced Ca++ release, the mechanisms related to spontaneous Ca++ release and to oxalate-facilitated inward Ca++ transport, as measured in this study, appear to be normal in SR from human MH skeletal muscle.

Calcium↗
PubMed1983

Prolonged electromechanical coupling time intervals in skeletal muscle of pigs susceptible to malignant hyperthermia.

Electromechanical properties of skeletal muscle were compared between malignant hyperthermia (MH)-susceptible and control pigs. These muscle properties were studied both in vivo and in vitro. The in vivo time interval from nerve stimulation to onset of mechanical tension was longer in muscle of pigs susceptible to MH. Kinetics of formation of the in vivo compound muscle action potential did not differ between pig groups, whereas the time from peak of the muscle action potential to tension onset was longer for MH muscle. In vitro the time from direct stimulation to tension onset was also longer for MH muscle. These results suggest that the mechanism causing longer electromechanical time intervals in MH skeletal muscle is distal to the myoneural junction. Data comparing contraction kinetics between muscle from MH and control pigs indicates that the mechanism contributing to the longer time interval involves the transfer of signal from the transverse tubule to the sarcoplasmic reticulum in the pigs studied.

Animals↗
PubMed1983

Spectrum of susceptibility to malignant hyperthermia--diagnostic dilemma.

Utilizing established in vitro muscle contracture tests, we have identified three diagnostic contracture phenotypes for malignant hyperthermia susceptibility (MHS) among 103 patients. Phenotype H is an unequivocal diagnostic result for MHS, as is the nonsusceptible phenotype N. The third diagnostic group, phenotype K, represents an equivocal diagnostic response. To provide a basis for understanding relationships between contracture phenotypes and MHS, pigs with phenotypes H, K, and N were exposed to a standardized anesthetic protocol for assessing MHS. During the anesthetic challenge, phenotype H pigs developed a more severe form of the MH syndrome than did phenotype K pigs. Comparing phenotype H v K average responses, VO2 increased four- v twofold; lactate increased 13- v 9-fold; and temperature increased 41.7 degrees C v 39.2 degrees C, respectively. These values either had no change or decreased in the phenotype N pigs. Results of this study suggest that a spectrum of MHS exists among the human population.

Animals↗
PubMed1982

Masseter spasm induced by succinylcholine in children: contracture testing for malignant hyperthermia: report of six cases.

We evaluated six boys who had developed isolated masseter muscle spasm following intravenous succinylcholine. All were receiving halothane by inhalation.l In vitro muscle contracture tests utilizing halothane and caffeine were performed. Four of the six boys had contracture response similar to those of malignant hyperthermia susceptible patients. Rigidity following succinylcholine should prompt the clinician to consider malignant hyperthermia but has been associated with other myopathic conditions as discussed.

Anesthesia↗
PubMed1980

Porcine malignant hyperthermia--failure of dantrolene dose response to diagnose susceptibility (halothane effect).

Dantrolene, a skeletal muscle relaxant, has been proven prophylactic and therapeutic for malignant hyperthermia (MH) in swine. This study examined the feasibility of using a dantrolene dose response as measured by indirectly evoked foretoe twitch depression as a means to safely discriminate MH susceptibility in swine. The effect of halothane on the dantrolene response was quantified. Subjects were five Poland China malignant hyperthermia susceptible (MHS) and five Hampshire malignant hyperthermia resistant (MHR) swine. Dantrolene dose response was determined twice in each anaesthetized subject, once with thiopentone and subsequently with thiopentone and halothane. Dantrolene in incremental doses, 0.15 mg.kg-1, was given to a cumulative dose of 2--3 mg.kg-1. Under thiopentone anaesthesia, the dantrolene dose responses were similar in MHS and MHR animals. The presence of halothane augmented dantrolene twitch depression in MHS but not MHR animals when compared to their response under thiopentone. Under halothane, the MHS animals had significantly augmented dantrolene response compared to MHR pigs, but three MHS animals had developed the MH syndrome prior to receiving dantrolene. We conclude that dantrolene muscle relaxant dose response cannot be used as a diagnostic test for MHS in swine. Halothane augments dantrolene twitch depression in MHS swine.

Animals↗
PubMed1980

Dantrolene dose response in malignant hyperthermia-susceptible (MHS) swine: method to obtain prophylaxis and therapeusis.

The authors examined the thesis that a dose of dantrolene producing 95 per cent of maximal muscle relaxation (ED95) would effectively prevent or treat malignant hyperthermia (MH). In one group of four pigs sensitive to malignant hyperthermia (MHS) a dose response to intravenous dantrolene was determined by quantitation of toe twitch tension. From these data, the ED95 relaxant dose (3.5 mg/kg) was derived. In a second group of four MHS pigs, the ED95 dantrolene dose was administered prior to MH challenge with succinylcholine, 2 mg/kg, and halothane, 1.5 per cent. MH was prevented in each animal, while measurements of arterial pressure, arterial blood-gas, pH and lactate values, rectal temperature, and heart rate were done. Later, MH rapidly developed in the same four animals when they were again challenged. When treated with the ED95 dose, each animal survived. Finally, each pig was challenged without dantrolene prophylaxis or therapeusis, and all succumbed from MH. Previous studies have shown the efficacious use of dantrolene in prevention or treatment of porcine MH, but doses used have varied, without rationale. The present study shows that in MHS pigs the ED95 muscle relaxant dose of dantrolene (3.5 mg/kg) successfully prevents and treats MH.

Animals↗