The effect of haloperidol, spiperone and dantrolene on the concentrations of creatine phosphate, ATP and lactate in brain and skeletal muscle of the rat during halothane anesthesia.

The concentrations of creatine phosphate, ATP and lactate were measured in the brain and skeletal muscle of rats under halothane anesthesia (1 to 2% in oxygen) and in animals either premedicated with haloperidol or spiperone (200 mg kg-1 and 2 mg kg-1) or treated with dantrolene (860 mg kg-1). Haloperidol and spiperone had no effect on ATP or lactate in skeletal muscle, but caused more than a 30% increase in the concentration of creatine phosphate (p less than 0.01). With dantrolene, an 80% increase in creatine phosphate (p less than 0.0001) and a significant decrease in lactate (p less than 0.0001) were found. Haloperidol caused a significant decrease in brain creatine phosphate concentration (p less than 0.05) while at a dosage of 2 mg kg-1, the ATP concentration was higher (p less than 0.05). Spiperone (2 mg kg-1) caused a 19% increase in creatine phosphate (p less than 0.005) as well as a significant decrease in lactate (p less than 0.005). Dantrolene had no significant effect on the concentration of any brain metabolite. Our results indicate that the effect of anesthetics on the concentration of energy metabolites in tissues can be influenced by drug treatment, which may have implications in the choice of an anesthetic regimen to be used in tissue harvesting.

The effect of anaesthetics on the concentration of creatine phosphate, adenosine triphosphate and lactate in brain and skeletal muscle of the rat.

Rats were anaesthetized with ten anaesthetics. Ketamine and enflurane gave the lowest concentration of creatine phosphate and ATP and the highest of lactate in brain, while giving the highest concentration of the high-energy phosphates and the lowest of lactate in skeletal muscle. In general, intraperitoneally-administered anaesthetics gave higher concentrations of creatine phosphate and ATP and lower concentrations of lactate in brain than did the inhalant anaesthetics. The most rapid induction of anaesthesia was achieved with halothane and enflurane, while ketamine gave variable induction times and poor analgesia. Halothane stimulated glycolysis and lowered the concentrations of high-energy phosphates in skeletal muscle.

Metabolism of monoamines in malignant hyperthermia-susceptible pigs.

A comparison of monoamine oxidase activities in the hypothalamus and striatum between malignant hyperthermia-susceptible (Pietrain) and malignant hyperthermia-resistant (Landrace/Large White) pigs showed no significant difference between the two breeds. The concentrations of noradrenaline, dopamine and their non-O-methylated metabolites did not reflect the low activities of monoamine oxidase type A differentially. The malignant hyperthermia-susceptible pigs had significantly greater concentrations of 3,4-dihydroxyphenyl glycol in the striatum, and of 3,4-dihydroxymandelic acid in the hypothalamus. Consequently, in the brain, low monoamine oxidase type A activity does not appear to be involved in susceptibility to malignant hyperthermia. In addition, monoamine oxidase activities in the heart, liver, kidney and intestinal mucosa and catechol-O-methyl transferase activities in the kidney were the same in the susceptible and resistant pigs.

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.