Anesthesia and analgesia
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Anesthesia and analgesia · Aug 2000
Prednisolone-induced muscle dysfunction is caused more by atrophy than by altered acetylcholine receptor expression.
Large doses of glucocorticoids can alter muscle physiology and susceptibility to neuromuscular blocking drugs by mechanisms not clearly understood. We investigated the effects of moderate and large doses of prednisolone on muscle function and pharmacology, and their relationship to changes in muscle size and acetylcholine receptor (AChR) expression. With institutional approval, 35 Sprague-Dawley rats were randomly allocated to receive daily subcutaneous doses of 10 mg/kg prednisolone (P10 group), 100 mg/kg prednisolone (P100 group), or an equal volume of saline (S group) for 7 days. A fourth group of rats was pair fed (food restricted) with the P100 rats for 7 days (FR group). On Day 8, the nerve-evoked peak twitch tensions, tetanic tensions, and fatigability, and the dose-response curves of d-tubocurarine in the tibialis cranialis muscle were measured in vivo and related to muscle mass or expression of AChRs. Rate of body weight gain was depressed in the P100, FR, and P10 groups compared with the S group. Tibialis muscle mass was smaller in the P100 group than in the P10 or S groups. The evoked peak twitch and tetanic tensions were less in the P100 group than in the P10 or S groups, however, tension per milligram of muscle mass was greater in the P100 group than in the S group. The 50% effective dose of d-tubocurarine (microg/kg) in the tibialis muscle was smaller in the P10 (33.6 +/- 5.4) than in the S (61.9 +/- 5.0) or the P100 (71.3 +/- 9.6) groups. AChR expression was less in the P10 group than in the S group. The evoked tensions correlated with muscle mass (r(2) = 0.32, P < 0.001), however, not with expression of AChR. The 50% effective dose of d-tubocurarine did not correlate with muscle mass or AChR expression. Our results suggest that the neuromuscular dysfunction after prednisolone is dose-dependent, and derives primarily from muscle atrophy and derives less so from changes in AChR expression. ⋯ The mechanisms by which chronic glucocorticoid therapy alters neuromuscular physiology and pharmacology are unclear. We suggest that the observed effects are dose-dependent and derive primarily from muscle atrophy and derive less from changes in acetylcholine receptor expression.
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Anesthesia and analgesia · Aug 2000
Absorption of carbon dioxide by dry soda lime decreases carbon monoxide formation from isoflurane degradation.
This study was performed to determine whether the absorption of carbon dioxide (CO(2)) influences the formation of carbon monoxide (CO) from degradation of isoflurane in dry soda lime. Isoflurane (0. 5%), CO(2) (5%), a combination of the two in oxygen, and pure oxygen were separately passed through samples of 600 g of completely dried soda lime (duration of exposure, 60 min; flow rate, 5 L/min). Downstream of the soda lime, we measured concentrations of CO, isoflurane, and CO(2) as well as the gas temperature. CO(2) increased the peaks of CO concentration (842 +/- 81 vs 738 +/- 28 ppm) and shortened the rise time of CO to maximum values (12 +/- 2 vs 19 +/- 4 min). However, CO(2) inhibited total CO formation (99 +/- 10 vs 145 +/- 6 mL). At the same time, CO(2) absorption by the soda lime decreased in the presence of CO formation (from 21.4 +/- 0. 8 to 19.4 +/- 0.9 g). The temperature of the gases increased during the passage of both isoflurane and CO(2) (to 32.6 +/- 2.0 degrees C and 39.4 +/- 4.0 degrees C, respectively), but the largest increase (to 41.5 +/- 2.1 degrees C) was recorded when isoflurane and CO(2) simultaneously passed through the dry soda lime. We assume that the simultaneous reduction in CO formation and CO(2) absorption is caused by the competition for the alkali hydroxides present in most of soda lime brands. ⋯ We determined, in vitro, that carbon monoxide (CO) formation from isoflurane by dry soda lime is reduced by carbon dioxide (CO(2)). We believe that the potential for injury from CO is less in the clinical milieu than suggested by data from experiments without CO(2) because of an interdependence between CO formation and CO(2) absorption.
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Anesthesia and analgesia · Aug 2000
A correlation between dexmedetomidine-induced biphasic increases in free cytosolic calcium concentration and energy metabolism in astrocytes.
The alpha(2)-adrenergic agonist, dexmedetomidine, increases free cytosolic calcium concentration ([Ca(2+)](i)) in astrocytes, but not in neurons. The present study was performed to characterize the origin of the increased Ca(2+) in mouse astrocytes cultured from the cerebral cortex, the dose dependence of the effect, and its functional consequences. The increase in [Ca(2+)](i) was independent of extracellular Ca(2+), but was inhibited by dantrolene, showing that it is derived from intracellular stores; two peaks in [Ca(2+)](i) were demonstrated-one around 100 nM dexmedetomidine and the other in the low micromolar range. A similar dose dependence was found for pyruvate dehydrogenation, the initial metabolic reaction of oxidative degradation of pyruvate, suggesting that the these events are interrelated. The alpha(2)-adrenergic antagonist, yohimbine, abolished the metabolic stimulation at both peaks. However, whereas the increase in [Ca(2+)] (i) at 100 nM is abolished by yohimbine, increase in the micromolar range was partly inhibited by yohimbine and partly by idazoxan, an inhibitor at the imidazoline-preferring site. The stimulation of energy metabolism in cerebrocortical astrocytes may explain the repeated finding that dexmedetomidine does not decrease oxidative metabolism in the brain in vivo. The functional importance of the additional imidazoline receptor-mediated increase in [Ca(2+)](i) at large dexmedetomidine concentrations is unknown. ⋯ Cytosolic calcium concentration and metabolism were measured in cultured astrocytes, the predominant glial cells. The results suggest that dexmedetomidine may owe its anesthetic effects to a Ca(2+)-dependent increase in astrocytic energy metabolism, allowing these cells to more effectively remove extracellular glutamate and potassium ions, and thus, decreasing neuronal excitability.