Body temperature control and arterial gases during halothane anaesthesia in the rat

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1. Rates and rate coefficients of glucose utilization and replacement were determined with [5-3H]- and [U-14C]-glucose in rats starved for 24h, either conscious or under halothane anaesthesia, in a thermoneutral environment. Plasma insulin concentrations were also measured. 2. Halothane anaesthesia decreased the turnover rate by 20%, which was similar to previously reported decreases in metabolic rates caused by natural sleep. 3. Fractional recycling of glucose carbon was little affected by halothane. 4. Comparison of values in one rat with those in another, among both conscious rats and those under halothane anaesthesia, showed that rate coefficients were inversely correlated with plasma glucose concentrations. 5. These findings indicated that halothane, in the concentration used (1.25%, v/v), had little specific effect on glucose metabolism. 6. Although equilibrium plasma glucose concentrations in different rats under halothane were widely different (4-8 mmol/l) the rates of utilization were very similar (2.5-3.1 micronmol/min per 100 g), indicating that these rates were determined by the production of glucose from gluconeogenic precursors released by basal metabolism, the rate of which is necessarily similar in different rats. 7. Among rats under halothane anaesthesia plasma insulin concentrations were negatively correlated with rate coefficients, showing that the differences between rate coefficients were mostly accounted for by differences between rats in tissue sensitivities to insulin. Thus in each 24h-starved rat, sleeping or resting, the main regulators of the plasma glucose concentrations were the rate of supply of gluconeogenic substrates from energy metabolism and the intrinsic sensitivity of the tissues to insulin. 8. We found that a commonly used deionization method of purifying glucose for determination of its specific radioactivity was inadequate.

“…The design of the experiments was controlled by findings on the effects of halothane on core temperature and arterial Pco2 and pH (Heath & Rose, 1976).…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Rates of glucose utilization and glucogenesis in rats in the basal state induced by halothane anaesthesia

Heath¹,

Frayn²,

Rose³

1977

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“…220-241 g) that had been maintained for at least 3 weeks at 20°C ambient with 12h light/day were starved for 24h before use. Each rat was anaesthetized with halothane, and ambient temperature was adjusted to maintain the colon temperature at 37-38°C (Heath & Rose, 1976). For infusion experiments a cannula was inserted into a lateral tail vein, and another, for blood sampling, into a tail artery (Agrelo & Dawson, 1968).…”

Section: Animal Experimentsmentioning

confidence: 99%

“…We therefore set out to explore the possibility of modelling the relevant pathways in vivo under the most controllable conditions we could contrive, i.e. infusion of [14C]bicarbonate to a steady isotopic state into the rat in the basal state, induced by halothane anaesthesia and 24h starvation (Denckla, 1970;Heath & Rose, 1976). This system provided an additional challenge, because it was closely analogous to one of those used in a thorough kinetic study of hepatocytes by Mullhofer et al (1977a,b), who could not account for their findings with this substrate by accepted pathways.…”

mentioning

confidence: 99%

[14C]bicarbonate fixation into glucose and other metabolites in the liver of the starved rat under halothane anaesthesia. Metabolic channelling of mitochondrial oxaloacetate

Heath¹,

Rose²

1985

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Previous attempts to account for the labelling in vivo of liver metabolites associated with the citrate cycle and gluconeogenesis have foundered because proper allowance was not made for the heterogeneity of the liver. In the basal state (anaesthetized after 24h starvation) this heterogeneity is minimal, and we show that labelling by [14C]bicarbonate can be interpreted unambiguously. [14C]Bicarbonate was infused to an isotopic steady state, and measurements were made of specific radioactivities of blood bicarbonate, alanine, glycerol and lactate, of liver alanine and lactate, and of individual carbon atoms in blood glucose and liver aspartate, citrate and malate. (Existing methods for several of these measurements were extensively modified.) The results were combined with published rates of gluconeogenesis, uptake of gluconeogenic precursors by the liver, and citrate-cycle flux, all measured under similar conditions, and with estimates of other rates made from published data. To interpret the results, three ancillary measurements were made: the rate of CO2 exchange by phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) under conditions that simulated those in vivo; the 14C isotope effect in the pyruvate carboxylase (EC 6.4.1.1) reaction (14C/12C = 0.992 +/- 0.008; S.E.M., n = 8); the ratio of labelling by [2-14C]- to that by [1-14C]-pyruvate of liver glutamate 1.5 min after injection. This ratio, 3.38, is a measure of the disequilibrium in the mitochondria between malate and oxaloacetate. The data were analysed with due regard to experimental variance, uncertainties in values of fluxes measured in vitro, hepatic heterogeneity and renal glucose output. The following conclusions were reached. The results could not be explained if CO2 fixation was confined to pyruvate carboxylase and there was only one, well-mixed, pool of oxaloacetate in the mitochondria. Addition of the other carboxylation reactions, those of PEPCK, isocitrate dehydrogenase (EC 1.1.1.42) and malic enzyme (EC 1.1.1.40), was not enough. Incomplete mixing of mitochondrial oxaloacetate had to be assumed, i.e. that there was metabolic channelling of oxaloacetate formed from pyruvate towards gluconeogenesis. There was some evidence that malate exchange across the mitochondrial membrane might also be channelled, with incomplete mixing with that in the citrate cycle. Calculated rates of exchange of CO2 by PEPCK were in agreement with those measured in vitro, with little or no activation by Fe2+ ions.(ABSTRACT TRUNCATED AT 400 WORDS)

“…Arterial Pcoo2 values were determined in rats under halothane during 'rate' experiments. They were 59.3±6.3kPa (44.5±4.7Torr; S.D., 13 rats), about 70% higher than in earlier controls (Little & Threlfall, 1974;Heath & Rose, 1976), but very like those in starved rats under halothane. Within the group of rats under halothane Pco2 values were not correlated with rates or rate coefficients, but were weakly and positively correlated with terminal plasma glucose concentrations.…”

Section: Dependence Of Rate Coefficients and Rates On Terminal Plasmamentioning

confidence: 61%

Glucose turnover in the post-absorptive rat and the effects of halothane anaesthesia

Heath¹,

Frayn²,

Rose³

1977

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1. Rates and rate coefficients of glucose utilization and replacement in post-absorptive rats, either conscious or under halothane anaesthesia, were determined in a thermoneutral environment by using [5-3H]- and [U-14C]glucose. Label was not injected into rats under halothane until about 0.5h after anaesthesia was initiated. 2. Comparison with the results for 24h-starved rats in the preceding paper [Heath et al. (1977) Biochem. J. 162, 643-651] showed that insulin concentrations were considerably higher but rate coefficients for glucose utilization were little altered in post-absorptive rats. Sensitivity to insulin was thus considerably increased by a 24h period of starvation in the rat. 3. Fractional recycling of glucose carbon in post-absorptive rats was under one-half of that in starved rats, reflecting the larger contribution of liver glycogenolysis to glucose production in the former. 4. In post-absorptive rats halothane decreased the mean rate of glucose utilization by about 17%. This decrease was associated with an increase in mean plasma insulin concentration, showing that halothane decreased sensitivity to insulin. 5. Recycling was slightly increased by halothane, indicating that the contribution of liver glycogen to the total glucogenic rate was decreased, probably because liver glycogen concentration were about 40% lower throughout the rate determinations in halothane. 6. Comparison of our results with earlier work shows that during and shortly after induction of halothane anaesthesia glucose turnover must have been greatly increased whereas from about 0.5h after induction it was decreased.