Inhibitory effects of etomidate and ketamine on endothelium-dependent relaxation in canine pulmonary artery.
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BACKGROUND: The authors recently demonstrated that acetylcholine-induced pulmonary vasorelaxation had two primary components, nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). The goal was to investigate the effects of etomidate and ketamine on the NO- and EDHF-mediated components of pulmonary vasorelaxation in response to acetylcholine, bradykinin, and the calcium ionophore, A23187. METHODS: Canine pulmonary arterial rings with an intact endothelium were suspended in organ chambers for isometric tension recording. The effects of etomidate and ketamine (10(-5) M and 10(-4) M) on vasorelaxation responses to acetylcholine, bradykinin, and A23187 were assessed in phenylephrine-contracted rings. The NO- and EDHF-mediated components of relaxation were assessed using a NO synthase inhibitor (N-nitro-L-arginine methylester [L-NAME]: 10(-4) M) and a Ca2+-activated potassium channel inhibitor (tetrabutylammonium hydrogen sulfate [TBA]: 10(-3) M) in rings pretreated with a cyclooxygenase inhibitor (ibuprofen: 10(-5) M). Intracellular calcium concentration ([Ca2+]i) was measured in cultured bovine pulmonary artery endothelial cells loaded with acetoxylmethyl ester of fura-2. RESULTS: Etomidate and ketamine attenuated pulmonary vasorelaxation in response to acetylcholine and bradykinin, whereas they had no effect on the response to A23187. The relaxant responses to acetylcholine and bradykinin were attenuated by L-NAME or TBA alone and were abolished by combined inhibition in rings pretreated with ibuprofen. Etomidate and ketamine further attenuated both L-NAME-resistant and TBA-resistant relaxation. These anesthetics also inhibited increases in endothelial [Ca2+]i in response to bradykinin, but not A23187. CONCLUSION: These results indicate that etomidate and ketamine attenuated vasorelaxant responses to acetylcholine and bradykinin by inhibiting both NO- and EDHF-mediated components. Moreover, our results suggest that these anesthetics do not directly suppress NO or EDHF activity, but rather inhibit the endothelial [Ca2+]i transient in response to receptor activation. (+info)
Molecular pharmacology of T-type Ca2+ channels.
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Over the past few years increasing attention has been focused on T-type calcium channels and their possible physiological and pathophysiological roles. Efforts toward elucidating the exact role(s) of these calcium channels have been hampered by the lack of T-type specific antagonists, resulting in the subsequent use of less selective calcium channel antagonists. In addition, the activity of these blockers often varies with cell or tissue type, as well as recording conditions. This review summarizes a variety of compounds that exhibit varying degrees of blocking activity towards T-type Ca2+ channels. It is designed as an aid for researchers in need of antagonists to study the biophysical and pathological nature of T-type channels, as well as a starting point for those attempting to develop potent and selective antagonists of the channel. (+info)
Malignant hyperthermia in a patient with Graves' disease during subtotal thyroidectomy.
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We report the case of a 31-year-old man with Graves' disease who manifested malignant hyperthermia during subtotal thyroidectomy. His past medical history and family history were unremarkable. Before surgery, his condition was well controlled with propylthiouracil, beta-adrenergic blocker and iodine. During the operation, anesthesia was induced by intravenous injection of vecuronium and thiopental, followed by suxamethonium for endotracheal intubation. Anesthesia was maintained with nitrous oxide and sevoflurane. One hour after induction of anesthesia, his end tidal carbon dioxide concentration (ET(CO2)) increased from 40 to 50 mmHg, heart rate increased from 90 to 100 beats per min and body temperature began to rise at a rate of 0.3 degrees C per 15 min. Suspecting thyroid storm, propranolol 0.4 mg and methylprednisolone 1,500 mg were administered, which, however, had little effect. Despite the lack of muscular rigidity, the diagnosis of malignant hyperthermia was made based on respiratory acidosis. Sevoflurane was discontinued and dantrolene was given by intravenous bolus. Soon after the treatment, ET(CO2), heart rate and body temperature started to fall to normal levels. His laboratory findings showed abnormally elevated serum creatine phosphokinase and myoglobin but normal thyroid hormone levels. Since dantrolene is efficacious in thyrotoxic crisis and malignant hyperthermia, an immediate intravenous administration of dantrolene should be considered when a hypermetabolic state occurs during anesthesia in surgical treatment for a patient with Graves' disease. (+info)
Medications in the breast-feeding mother.
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Prescribing medications for a breast-feeding mother requires weighing the benefits of medication use for the mother against the risk of not breast-feeding the infant or the potential risk of exposing the infant to medications. A drug that is safe for use during pregnancy may not be safe for the nursing infant. The transfer of medications into breast milk depends on a concentration gradient that allows passive diffusion of nonionized, non-protein-bound drugs. The infant's medication exposure can be limited by prescribing medications to the breast-feeding mother that are poorly absorbed orally, by avoiding breast-feeding during times of peak maternal serum drug concentration and by prescribing topical therapy when possible. Mothers of premature or otherwise compromised infants may require altered dosing to avoid drug accumulation and toxicity in these infants. The most accurate and up-to-date sources of information, including Internet resources and telephone consultations, should be used. (+info)
Carotid endarterectomy; local or general anaesthesia?
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OBJECTIVES: to review the evidence for theoretical and clinical benefits of local or general anaesthesia for carotid endarterectomy. METHODS: literature review. RESULTS: animal studies suggest cerebral protection by a variety of general anaesthetic agents but clinical evidence is lacking. There is some clinical evidence that normal cerebral protective reflexes are preserved with local anaesthesia. Shunt insertion is the most widely used method of providing cerebral protection with awake testing the most reliable monitoring technique for the identification of ischaemia. There are therefore theoretical arguments for a reduced risk of perioperative stroke when local anaesthesia is used and this is supported by a meta-analysis of non-randomised studies. Intraoperative blood pressure is always higher with local anaesthesia but the incidence of postoperative haemodynamic instability seems to be independent of anaesthetic technique. There is little evidence that myocardial ischaemia is more common with either anaesthetic technique but meta-analysis of non-randomised again suggests fewer cardiac complications with local anaesthesia. Cranial nerve injury and haematoma formation may be less common with local anaesthesia but the evidence is weak. There is no evidence that surgery is more difficult with local anaesthesia or that it is poorly tolerated by the patients. CONCLUSIONS: there are theoretical arguments and clinical evidence that the outcome from carotid endarterectomy may be better when local anaesthesia is used with no significant disadvantages. An appropriately designed randomised trial is required to confirm this. (+info)
Mitosis in mammalian cells during exposure to anesthetics.
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The effects of methoxflurane, trichloroethylene, chloroform, halothane and diethyl ether on the division of Chinese hamster fibroblasts in spinner culture have been studied. All agents caused dose-dependent inhibition of cell multiplication. Halothane increased the cell cycle time roughly in accordance with its effect on multiplication rate. There was no evidence that mitosis was greatly prolonged, and only small numbers of "c-metaphases" were seen. However, exposure to halothane resulted in a marked and rapid reduction in the prophase count, suggesting prolongation of G2 (the post-synthetic phase). Cine-photo-micrography showed frequent delay in division of cytoplasm at mitosis, and many binucleate cells were seen. (+info)
[Renal effects and metabolism of sevoflurane in Fisher 3444 rats: an in-vivo and in-vitro comparison with methoxyflurane].
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Sevoflurane, 1.4 per cent (MAC), was administered to groups of Fischer 344 rats for 10 hours, 4 hours, or 1 hour; additional rats received 0.5 per cent methoxyflurane for 3 hours or 1 hour. Urinary inorganic fluoride excretion of sevoflurane in vivo was a third to a fourth that of methoxyflurane. However, using hepatic microsomes, sevoflurane and methoxyflurane were defluorinated in vitro at essentially the same rate. The discrepancy between defluorination of sevoflurane and methoxyflurane in vivo and in vitro was probably due to differences in tissue solubility between the drugs. There were no renal functional or morphologic defects following sevoflurane administration. An unexplained adverse effect was significant weight loss, which occurred following all exposures to sevoflurane. (+info)
Postoperative chronic renal failure: a new syndrome?
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Of 125 patients with postsurgical acute tubular necrosis, 87 died, 34 regained clinical normal renal function, and 4 survivors (9.5%) were left with severe permanent renal failure, two of whom required chronic dialysis and transplantation. Preoperatively these 4 patients had normal renal function. The 4 patients were above age 60, two had undergone methoxyflurane anesthesia, and nephrotoxic antibiotics were used in all. The incidence of permanent renal failure is much higher than ever reported and may reflect the survival of patients who previously died because of less ideal dialysis. We believe that the cause of this permanent lesion is multifactorial, including age (over 60 years), nephrotoxic antibiotics (particularly cephalothin and gentamicin sulfate), and nephrotoxic anesthetic (methoxyflurane) agents. This combination of factors should be avoided whenever possible. (+info)