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Biomedical subjects

A M Cheah

Publications and source records attributed to A M Cheah.

17 recordsLinked to original sources
PubMed1990

Calcium accumulation by sarcoplasmic reticulum in whole muscle homogenate preparations of malignant hyperthermia diagnostic patients and pigs.

Calcium accumulation by the sarcoplasmic reticulum in whole muscle homogenate preparations of malignant hyperthermia-susceptible (MH+) and non-susceptible (MH-) humans and pigs was investigated using a calcium electrode at 35 degrees C. Sarcoplasmic reticulum of MH+ humans and pigs showed normal Ca2+ accumulation, with no difference being observed in the rate and the time taken to achieve maximal accumulation. However, the capacity for Ca2+ accumulation by the sarcoplasmic reticulum in MH+ humans and pigs is considerably less stable than normal after prolonged ageing of the whole muscle homogenate preparations in ice. In MH+ patients, the capacity for Ca2+ accumulation by the sarcoplasmic reticulum showed a decline of 62% at 22 h ageing and 70% at 48 h ageing, as compared with a reduction of only 23% in MH- patients. In MH+ pigs, the sarcoplasmic reticulum showed a 96% deterioration in the capacity for Ca2+ accumulation as compared with a loss of only 40% in MH- pigs at 7 h ageing in ice. In both humans and pigs, the decline in Ca2+ accumulation was prevented by incubating the whole muscle homogenate preparations for 2 h at 35 degrees C prior to ageing the preparations. The diminished Ca2+ accumulating capacity of the sarcoplasmic reticulum in whole muscle homogenate preparations of MH-susceptible individuals in our experimental protocol provides a potential diagnostic test for malignant hyperthermia susceptibility.

Animals↗
PubMed1989

Skeletal muscle mitochondrial respiration of malignant hyperthermia-susceptible patients. Ca2+-induced uncoupling and free fatty acids.

1. Skeletal muscle mitochondria of malignant hyperthermia (MH)-susceptible patients showed normal oxidative phosphorylation but were more easily uncoupled than normal by exogenous Ca2+. 2. Fatty acids, in stimulating the mitochondrial ATPase activity, are responsible for the enhanced State 4 respiration in MH-susceptible patients. 3. These results imply that skeletal muscle mitochondria and free fatty acids are associated with the development of MH syndrome.

Calcium↗
PubMed1988

Lipid analysis of skeletal muscle from pigs susceptible to malignant hyperthermia.

Previous studies demonstrated that lipid profiles of humans and pigs susceptible to malignant hyperthermia (MH) differ from those of normal humans and pigs. Lipid extraction techniques retaining in vivo lipid profiles most closely were used in the present study to determine if stimulation of lipolysis by the processes of homogenization or extraction might account for the reported differences in lipid profiles. No differences were observed among three genotypes of British Landrace pigs with respect to cholesterol levels, triglyceride levels, or total lipid phosphorus values of whole muscle (longissimus dorsi). Phospholipid distributions were the same for all three groups. Individual free fatty acids and fatty acids acylated to triglycerides were similar among the genotypes. These results do not support altered lipid profiles in vivo in MH-susceptible swine. Previously used homogenization and extraction procedures most likely affect the lipolytic activity to a different extent in muscle from MH-susceptible pigs and normal pigs.

Animals↗
PubMed1985

Malignant hyperthermia: molecular defects in membrane permeability.

Malignant hyperthermia (MH), a genetically inherited disorder of skeletal muscle, is due to molecular defect in membrane permeability. The alteration in membrane permeability is suggested to be due to enhanced phospholipase A2 activity which is responsible for the increased level in sarcoplasmic Ca2+. The excess Ca2+ is responsible for muscle hyper-rigidity and enhanced rate of glycolysis, resulting in a rapid rate of lactic acid production and a low pH in MH muscle.

Animals↗
PubMed1985

Influence of environmental temperature and energy intake on porcine skeletal muscle mitochondria.

The influence of acclimation to a cold (10 degrees C) or warm (35 degrees C) environment on the functional characteristics of skeletal muscle mitochondria has been investigated in young pigs on a high (H) or low (L) energy intake. Living at 10 degrees C increased the amount of mitochondrial protein and the concentration of cytochrome. Ca2+-stimulated succinate oxidation by mitochondria from the 35H group was tightly coupled and similar to that in pigs living under normal husbandry conditions. Mitochondria from the three other groups were readily uncoupled and thus resembled those from pigs susceptible to malignant hyperthermia. Arrhenius plots of State 3 Ca2+-stimulated succinate oxidation showed that energy intake altered the transition temperature suggesting possible differences in the structure of the mitochondrial membrane.

Adenosine Diphosphate↗
PubMed1981

Mitochondrial calcium transport and calcium-activated phospholipase in porcine malignant hyperthermia.

The interaction of Ca2+ with mitochondria isolated from longissismus dorsi, a predominantly white skeletal muscle, of normal and malignant hyperthermia pigs was investigated using tightly-coupled preparations. Arrhenius plots of mitochondrial Ca2+ -stimulated respiration for succinate oxidation of malignant hyperthermia pigs showed a transition temperature (Tt) of 26.31 +/- 0.80 degrees C (n = 5), which was decreased by spermine to 15.41 +/- 0.69 degrees C (n = 3), a value very similar to that for normal pigs. No difference in either the Tt or in the activation energy (Ea) was observed between the two types of pigs when ADP was used instead of Ca2+. Mitochondria of malignant hyperthermia pigs were uncoupled at 40 degrees C by exogenous Ca2+ at 1221 +/- 301 (n = 9) nmol Ca2+ per mg proteinn during succinate oxidation and the uncoupled mitochondria showed large amplitude swelling. Both the Ca2+ -induced uncoupling and swelling were prevented by bovine serum albumin and by the phospholipase inhibitors, spermine and tetracaine. In contrast, mitochondria of normal pigs were still tightly coupled even after a total addition of 2313 +/- 287 (n = 5) nmol Ca2+ per mg protein and retained the original condensed configuration in the presence or absence of spermine and tetracaine. Mitochondria of malignant hyperthermia pigs contained significantly (P less than 0.001) higher quantities of endogenous Ca2+ and showed a significantly (P less than 0.001) faster FCCP-induced endogenous Ca2+ efflux rate than normal when monitored spectroscopically with murexide. No significant difference was observed in either the rate of exogenous Ca2+ uptake or in the extent of Ca2+ accumulated in the aerobic steady state during succinate oxidation between the two types of pigs. The rate of mitochondrial Ca2+ efflux of malignant hyperthermia pigs during anaerobiosis was about twice that of normal. Experimental evidence suggests that mitochondria from musculi longissimus dorsi of malignant hyperthermia pigs contained a Ca2+ -stimulated phospholipase A2 (EC 3.1.1.4, phosphatide 2-acylhydrolase), and that this enzyme if present in mitochondria of normal pigs is either latent or in very low concentration. The significance of the Ca2+ -stimulated phospholipase A2 and its association with the enhanced rate of glycolysis in porcine malignant hyperthermia syndrome and in the post-mortem formation of the pale, soft and exudative conditions observed in white skeletal muscles of malignant hyperthermia pigs is discussed.

Adenosine Diphosphate↗
PubMed1979

Mitochondrial calcium efflux and porcine stress-susceptibility.

Mitchondrial Ca2+ efflux rates of M. longissimus dorsi correlate very closely with parameters associated with porcine stress-susceptibility. Experimental data support the measurement of mitochondrial Ca+2 efflux to be a very sensitive and reliable method for differentiating porcine stress-susceptibility.

Animals↗