Effect of Inhalational Anesthetics on Cytotoxicity and Intracellular Calcium Differently in Rat Pheochromocytoma Cells (PC12)

Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in rat pheochromocytoma cells （PC12） in a concentration- and time-dependent manner with unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum （ER） via activation of inositol 1,4,5-trisphosphate （IP3） receptors. Alzheimer＇s presenilin-1 （PS 1） mutation increased activity of IP3 receptors and therefore rendered cells vulnerable to isoflurane-induced cytotoxicity. Sevoflurane and desflurane had less ability to disrupt intracellular calcium homeostasis and thus being less potent pared the cytotoxic effects of various inhaled to cause cytotoxicity. This study examined and com-anesthetics on PC12 cells transfected with the Alzheimer＇s mutated PS 1 （L286V） and the disruption of intracellular calcium homeostasis. PC 12 cells transfected with wild type （WT） and mutated PS 1 （L286V） were treated with equivalent of 1 MAC of isoflurane, sevoflurane and desflurane for 12 h. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in cytosolic space （[Ca^2＋]c） were determined after exposing different types of cells to various inhalational anesthetics. The effects of IP3 receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in L286V PC12 cells were also determined. The results showed that isoflurane at 1 MAC for 12 h induced cytoxicity in L286V but not WT PC12 cells, which was also associated with greater and faster elevation of peak [Ca^2＋]c in L286V than in the WT cells. Xestospongin C significantly ameliorated isoflurane cytotoxicity in L286V cells, as well as inhibited the calcium release from the ER in L286V cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar cytotoxicity or elevation of peak [Ca^2＋]c in L286V PC 12 cells. These results suggested that isoflurane induced cytoxicity by partially causing abnormal calcium release from the ER via activation of IP3 receptors in L286V PC12 cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar elevation of [Ca^2＋]c or neurotoxicity in PC 12 cells transfected with the Alzheimer＇s PS 1 mutation.

耳内镜联合七氟醚吸入麻醉用于儿童耵聍取出术

研究回顾性分析门诊耵聍栓塞患儿在硬性耳内镜联合七氟醚吸入麻醉下,应用耳科显微手术器械进行耵聍取出术。

Isoflurane Enhances the Expression of Cytochrome C by Facilitation of NMDA Receptor in Developing Rat Hippocampal Neurons In Vitro

This study examined the effects of clinically relevant concentrations of isoflurane on the amplitude of NMDA receptor current （INMDA） and the expression of cytochrome C in cultured developing rat hippocampal neurons. The hippocampi were dissected from newborn Sprague-Dawley rats. Hippocampal neurons were primarily cultured for 5 days and then treated with different concentrations of isoflurane [（0.25, 0.5, 0.75, 1 minimum alveolar concentration （MAC））]. The peak of INMDA was re- corded by means of the whole cell patch clamp technique. The cytochrome C level was detected by Western blotting and quantitative real-time PCR. Our results showed that isoflurane （0.25, 0.5, 0.75 and 1 MAC） potentiated the amplitude of INMDA by （116±8.8）%, （122±11.7）%, （135±14.3）% and （132~14.6）%, respectively, and isoflurane increased the mRNA expression of cytochrome C in a concentration-dependent manner. The cytochrome C mRNA expression reached a maximum after 0.5 MAC isoflurane stimulation for 6 h （P〈0.05）. It was concluded that isoflurane enhances the expression of cytochrome C in cultured rat hippocampal neurons, which may be mediated by facilitation of NMDA receptor.

Evaluation of high-concentration sevoflurane for induction and nasotracheal intubation without muscle relaxant for infants with different pulmonary blood flow undergoing surgery for congenital heart diseases

Background Inhalational anesthesia with sevoflurane for endotracheal intubation without muscle relaxant is now used widely for pediatric patients. This study assessed the efficacy and safety of induction with high concentration sevoflurane and of nasotracheal intubation without muscle relaxant in infants with increased or decreased pulmonary blood flow （PBF） and undergoing surgery for congenital heart diseases. Methods Fifty-five infants aged 2-12 months, weighing 4.7-10.0 kg, and scheduled for congenital cardiac surgery were enrolled. Subjects were divided into those with increased （IPBF group, n--29） and decreased （DPBF group, n=26） pulmonary blood flow. All infants received inhalational induction with 8% sevoflurane in 100.0% oxygen at a gas flow rate of 6 L/min. Nasotracheal intubation was performed 4 minutes after induction. Sevoflurane vaporization was decreased to 4.0% for placement of a peripheral intravenous line and invasive hemodynamic monitors. Five minutes later, sedatives and muscle relaxant were administered and the vaporizer was adjusted to 2% for maintenance of anesthesia. Bispectral index （BIS） scores, circulatory parameters, satisfactory and successful intubation ratios, adverse reactions, and complications of intubation were recorded. Results Times to loss of lash and pain reflexes were longer for the DPBF group （P 〈0.01）. Satisfactory intubation ratios were 93.1% and 61.5% for the I PBF and DPBF groups, respectively （P=0.008）. Successful intubation ratios were 96.6% and 76.9% for the IPBF and DPBF groups, respectively （P=0.044）. Following sevoflurane inhalation, blood pressures decreased significantly in the IPBF group but remained stable in the DPBF group. BIS scores declined to similar stable values, and a ＂nadir BIS＂ was recorded for both groups. No obvious adverse reactions or complications of intubation were noted perioperatively. Conclusions Induction with high concentration sevoflurane, although faster for infants with IPBF, is safe for infants with IPBF or DPBF. However, nasotracheal intubation without muscle relaxant after induction with high concentration sevoflurane is less successful and less satisfactory for infants with DPBF and should be used with caution in this patient group.

A comparison between vital capacity induction and tidal breathing induction techniques for the induction of anesthesia and compound A production

Background Vital capacity induction and tidal breathing induction are currently administered for inhalation induction of anesthesia with sevoflurane. The aim of this study was to compare them using sevoflurane with respect to induction time,complications of inhalation induction, and compound A production in adult patients.Methods Fifty-one women with American Society of Anesthesiologists physical status Ⅰ-Ⅱ undergoing mammary gland tumorectomy were randomly assigned to receive either vital capacity induction or tidal breathing induction with 8% sevoflurane at 6 L/min followed by laryngeal mask airway insertion. Induction times, complications of inhalation induction,and vital signs were recorded. Inspired concentrations of compound A were assayed and sofnolime temperatures were monitored at one-minute intervals after sevoflurane administration.Results The time to loss of eyelash reflex was significantly shorter with the vital capacity induction technique than with the tidal breathing induction technique （（43.8±13.4） seconds vs. （70.8±16.4） seconds, respectively; P 〈0.01）.Cardiovascular stability was similar in both groups. The incidence of complications was significantly less with the vital capacity induction technique than with the tidal breathing induction technique （7.7% vs. 32%, respectively; P 〈0.01）.However, the mean and maximum concentrations of compound A during induction were significantly higher in the vital capacity group than those in the tidal breathing group （P 〈0.05）; compound A concentration at the beginning of anesthesia maintenance was （40.73±10.83） ppm in the vital capacity group and （29.45±7.51） ppm in tidal breathing group （P=0.019）.Conclusion For inhalation induction of anesthesia, the vital capacity induction was faster and produced fewer complications than that for tidal breathing induction, but increased compound A production in the circuit system.