Methods: Sixty-one [alpha]-chloralose-anesthetized rabbits were instrumented for measurement of left ventricular (LV) pressure (tip-manometer), cardiac output (ultrasonic flowprobe), and myocardial infarct size (triphenyltetrazolium staining). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits of all six groups underwent a treatment period consisting of either no intervention for 35 min (control group, n = 11) or 15 min of isoflurane inhalation (1 minimum alveolar concentration end-tidal concentration) followed by a 10-min washout period (isoflurane group, n = 12). Four additional groups received the radical scavenger N-(2-mercaptoproprionyl)glycine (MPG; 1 mg [middle dot] kg-1 [middle dot] min-1) or Mn(III)tetrakis(4-benzoic acid)porphyrine chloride (MnTBAP; 100 [mu]g [middle dot] kg-1 [middle dot] min-1) during the treatment period with (isoflurane + MPG; n = 11; isoflurane + MnTBAP, n = 9) or without isoflurane inhalation (MPG, n = 11; MnTBAP, n = 7).
Results: Hemodynamic baseline values were not significantly different between groups (LV pressure, 97 +/- 17 mmHg [mean +/- SD]; cardiac output, 228 +/- 61 ml/min). During coronary artery occlusion, LV pressure was reduced to 91 +/- 17% of baseline and cardiac output to 94 +/- 21%. After 2 h of reperfusion, recovery of LV pressure and cardiac output was not significantly different between groups (LV pressure, 83 +/- 20%; cardiac output, 86 +/- 23% of baseline). Infarct size was reduced from 49 +/- 17% of the area at risk in controls to 29 +/- 19% in the isoflurane group (P = 0.04). MPG and MnTBAP themselves had no effect on infarct size (MPG, 50 +/- 14%; MnTBAP, 56 +/- 15%), but both abolished the preconditioning effect of isoflurane (isoflurane + MPG, 50 +/- 24%, P = 0.02; isoflurane + MnTBAP, 55 +/- 10%, P = 0.001). 相似文献
Methods: With Institutional Review Board approval, 24 consenting adult surgical patients were given either lorazepam or midazolam in a double-blind fashion (together with either intravenous fentanyl or epidural morphine for analgesia) through target-controlled intravenous infusions titrated to maintain a moderate level of sedation for 12-72 h postoperatively. Moderate sedation was defined as a Ramsay Sedation Scale score of 3 or 4. Sedation scores were measured, together with benzodiazepine plasma concentrations. Population pharmacokinetic and pharmacodynamic parameters were estimated using nonlinear mixed-effects modeling.
Results: A two-compartment model best described the pharmacokinetics of both lorazepam and midazolam. The pharmacodynamic model predicted depth of sedation for both midazolam and lorazepam with 76% accuracy. The estimated sedative potency of lorazepam was twice that of midazolam. The predicted C50,ss (plasma benzodiazepine concentrations where P(Sedation >= ss) = 50%) values for midazolam (sedation score [SS] >= n, where n = a Ramsay Sedation Score of 2, 3, . . . 6) were 68, 101, 208, 304, and 375 ng/ml. The corresponding predicted C50,ss values for lorazepam were 34, 51, 104, 152, and 188 ng/ml, respectively. Age, fentanyl administration, and the resolving effects of surgery and anesthesia were significant covariates of benzodiazepine sedation. The relative amnestic potency of lorazepam to midazolam was 4 (observed). The predicted emergence times from sedation after a 72-h benzodiazepine infusion for light (SS = 3) and deep (SS = 5) sedation in a typical patient were 3.6 and 14.9 h for midazolam infusions and 11.9 and 31.1 h for lorazepam infusions, respectively. 相似文献
Methods: The authors examined (1) the effects of BLA on neuronal voltage-gated Na+ channels in vitro under the whole cell patch clamp configuration and (2) the sensory and motor functions of rat sciatic nerve after single BLA injections in vivo.
Results: BLA at 10 [mu]m did not affect neuronal Na+ currents in clonal GH3 cells when stimulated infrequently to +50 mV. When stimulated at 2 Hz for 1,000 pulses (+50 mV for 4 ms), BLA reduced the peak Na+ currents by more than 90%. This use-dependent reduction of Na+ currents by BLA reversed little after washing. Single injections of BLA (0.2 ml at 0.375 mm) into the rat sciatic notch not only blocked sensory and motor functions of the sciatic nerve but also induced hyperexcitability, followed by sedation, arrhythmia, and respiratory distress. When BLA at 0.375 mm was coinjected with 2% lidocaine (approximately 80 mm) or epinephrine (1:100,000) to reduce drug absorption by the bloodstream, the sensory and motor functions of the sciatic nerve remained fully blocked for approximately 4 h and regressed completely after approximately 7 h, with minimal systemic effects. 相似文献
Methods: Fifteen healthy volunteers were enrolled. Two subjects were administered four inhalations of 2.2 mg morphine each at 1-min intervals or 4.4 mg over 3 min by intravenous infusion. Thirteen subjects were given twice the above doses, i.e., eight inhalations or 8.8 mg intravenously over 7 min. Arterial blood sampling was performed every minute during administration and at 2, 5, 7, 10, 15, 20, 45, 60, 90, 120, 150, 180, and 240 min after administration. The effect of morphine was assessed by measuring pupil diameter and ventilatory response to a hypercapnic challenge. Pharmacokinetic and pharmacodynamic analyses were performed simultaneously using mixed-effect models.
Results: The pharmacokinetic data after intravenous administration were described by a three-exponent decay model preceded by a lag time. The pharmacokinetic model for administration by inhalation consisted of the three-exponent intravenous pharmacokinetic model preceded by a two-exponent absorption model. The authors found that, with administration by inhalation, the total bioavailability was 59%, of which 43% was absorbed almost instantaneously and 57% was absorbed with a half-life of 18 min. The median times to the half-maximal miotic effects of morphine were 10 and 5.5 min after inhalation and intravenous administration, respectively (P < 0.01). The pharmacodynamic parameter ke0 was approximately 0.003 min-1. 相似文献
Methods: In vitro, freshly isolated alveolar type II cells were exposed to halothane during 4 h (1, 2, 4%) and 8 h (1%), and to thiopental during 4 h (10, 100 [mu]m) and 8 h (100 [mu]m). In vivo, rats were anesthetized with intraperitoneal thiopental or inhaled 1% halothane and mechanically ventilated for 4 or 8 h. SP-C mRNA expression was evaluated by ribonuclease protection assay.
Results: In vitro, 4-h exposure of alveolar type II cells to thiopental 10 and 100 [mu]m increased their SP-C mRNA content to 145 and 197%, respectively, of the control values. In alveolar type II cells exposed for 4 h to halothane 1, 2, and 4%, the SP-C mRNA content increased dose-dependently to 160, 235, and 275%, respectively, of the control values. In vivo, in mechanically ventilated rats, 4 h of halothane anesthesia decreased the lung SP-C mRNA content to 53% of the value obtained in control (nonanesthetized, nonventilated) animals; thiopental anesthesia increased to 150% the lung SP-C mRNA content. 相似文献
Methods: Payments from Medicare were compared with payments from other third parties in each clinical procedural terminology (CPT) grouping used by the West Virginia University Department of Anesthesiology during 1998. Changes in total Department of Anesthesiology receipts were determined if non-Medicare third-party payers paid Medicare rates. Then, the effect of adding payments at Medicare rates from patients without insurance was determined. Finally, potential changes in receipts of the Departments of Anesthesiology, Radiology, Surgery, and Medicine were compared by considering only patients with insurance and recalculating total payments to the departments using Medicare rates.
Results: Medicare paid less than other third-party payers in every clinical procedural terminology group. Total Department of Anesthesiology payments would decrease by 31% if all non-Medicare third-parties paid Medicare rates. Adding payments at Medicare rates from patients without insurance still leads to a 21% decrease in total Department of Anesthesiology receipts. Considering only patients with third-party coverage, Medicare-rate payments would decrease total Department of Anesthesiology payments by 37%, whereas radiology, surgery, and medicine payments would decrease by 26, 22, and 13% respectively. 相似文献
Methods: Canine pulmonary arterial rings were suspended for isometric tension recording. Intracellular calcium concentration ([Ca2+]i) was measured in pulmonary arterial strips loaded with acetoxylmethyl ester of fura-2. After phenylephrine-induced contraction, propofol (10-7 to 10-4 m) was administered in the presence or absence of the cyclooxygenase inhibitor ibuprofen (10-5 m). The effects of propofol on the arachidonic acid and prostacyclin relaxation-response curves were assessed. The amount of 6-keto prostaglandin F1[alpha](stable metabolite of prostacyclin) released from pulmonary vascular smooth muscle in response to phenylephrine was measured with enzyme immunoassay in the presence or absence of propofol and ibuprofen.
Results: Propofol potentiated phenylephrine-induced contraction in pulmonary arterial rings in a concentration-dependent and endothelium-independent manner. In endothelium-denuded strips, propofol (10-4 m) increased tension by 53 +/- 11%, and increased [Ca2+]i by 56 +/- 9%. Ibuprofen also potentiated phenylephrine-induced contraction but abolished the propofol-induced increases in tension and [Ca2+]i. Propofol had no effect on the relaxation response to prostacyclin, whereas propofol and ibuprofen attenuated the relaxation response to arachidonic acid to a similar extent. Phenylephrine markedly increased 6-keto prostaglandin F1[alpha] production, and this effect was virtually abolished by propofol and ibuprofen. 相似文献
Methods: Human Jurkat T-lymphoma cells overexpressing the antiapoptotic protein B-cell lymphoma 2 as well as cells deficient of caspase 9, caspase 8, or Fas-associated protein with death domain were exposed to lidocaine and compared with parental cells. The authors evaluated cell viability, mitochondrial alterations, cytochrome c release, caspase activation, and early apoptosis. Apoptosis was in addition investigated in neuroblastoma cells.
Results: In Jurkat cells, lidocaine reduced viability, associated with a loss of the mitochondrial membrane potential. At low concentrations (3-6 mm) of lidocaine, caspase 3 was activated and release of cytochrome c was detected, whereas at higher concentrations (10 mm), no caspase activation was found. Apoptosis by lidocaine was strongly reduced by B-cell lymphoma-2 protein overexpression or caspase-9 deficiency, whereas cells lacking the death receptor pathway components caspase 8 and Fas-associated protein with death domain were not protected and displayed similar apoptotic alterations as the parental cells. Lidocaine also induced apoptotic caspase activation in neuroblastoma cells. 相似文献
Methods: In a mouse neuronal-glial cell coculture, injury was provoked either by NMDA, glutamate, or oxygen deprivation and assessed by the release of lactate dehydrogenase into the culture medium. Increasing concentrations of either xenon or nitrogen (10-75% of an atmosphere) were coadministered and maintained until injury was assessed. In separate in vivo experiments, rats were administered N-methyl-dl-aspartate and killed 3 h later. Injury was quantified by histologic assessment of neuronal degeneration in the arcuate nucleus of the hypothalamus.
Results: Xenon exerted a concentration-dependent protection against neuronal injury provoked by NMDA (IC50 = 19 +/- 6% atm), glutamate (IC50 = 28 +/- 8% atm), and oxygen deprivation (IC50 = 10 +/- 4% atm). Xenon (60% atm) reduced lactate dehydrogenase release to baseline concentrations with oxygen deprivation, whereas xenon (75% atm) reduced lactate dehydrogenase release by 80% with either NMDA- or glutamate-induced injury. In an in vivo brain injury model in rats, xenon exerted a concentration-dependent protective effect (IC50 = 78 +/- 8% atm) and reduced the injury by 45% at the highest xenon concentration tested (75% atm). 相似文献
Methods: Four hundred thirty-two healthcare workers with occupational exposure to natural rubber latex were screened using a clinical history questionnaire and latex-specific immunoglobulin E serology. Genomic DNA was extracted from peripheral blood lymphocytes and analyzed for single-nucleotide polymorphisms in candidate genes of interest. Data from cases and controls were analyzed by nominal logistic regression, with P < 0.05 considered significant.
Results: The latex allergy phenotype was significantly associated with promoter polymorphisms in IL13 -1055 (P = 0.02), IL18 -607 (P = 0.02), and IL18 -656 (P = 0.02) compared with nonatopic controls. 相似文献
Methods: Malignant hyperthermia trigger-free general anesthesia was performed in MHS and MHN swine. Skeletal muscle specimens were excised for an in vitro contracture test with 0.6 mm enoximone. Thereafter, MHS and MHN swine were exposed to cumulative administration of 0.5, 1, 2, 4, 8, 16, and 32 mg/kg enoximone intravenously. Clinical occurrence of MH was defined by a Pco2 greater than 70 mmHg, a pH less than 7.20, and an increase in body temperature of more than 2.0[degrees]C.
Results: Enoximone induced marked contractures in all MHS muscle specimens in vitro. In contrast, only small or no contracture development was observed in MHN muscle specimens, without an overlap in contractures between MHS and MHN muscles. However, in vivo, no clinical differences were found between MHS and MHN swine following cumulative enoximone doses. According to the defined criteria, none of the swine developed MH during the experiment. Furthermore, high enoximone doses induced progressive circulatory insufficiency, and after receiving 32 mg/kg enoximone, all animals died of cardiovascular failure. 相似文献