143 Pharmacology Results and Discussion: An increase of relative resistance which is the indicator of red blood cell deformability was detected in rats applied to IR. Deformability index was similar in GroupC and GroupIRD (p=0574). It was significantly increased in Group IR when compared to GroupC and IRD (p=0.005,p=0.028). MDA activit y was higher in GroupIR when compared to Group C and IRD (p=0.027,p=0.011). . SOD activit y was significantly in- creased in GroupIR when compared to Group C (p=0.029). Conclusion(s): Ery throcy te deformability was damaged in rats having IR in- jur y and this might be because of increased lipid peroxidation of er y throcy te. MDA accumulation as a result of lipid peroxidation in er y throcy tes may cause deterioration of deformability of ery throcy tes and rapidly aging in ery thro- cy tes. So measurement of er y throcy te deformabilit y might be useful in follow- up of IR injury as a parameter. It was shown that dexmedetomidine may be useful in decreasing the adverse ef fects of this injury. However these findings should be suppor ted by detailed clinical and experimental studies. 9AP6-8 Ef fect of esmolol on propofol consumption in patients undergoing craniotomy Asouhidou I., Samaras A., Katsaridis V., Ioannou P . ‚G.Papanikolaou‘, Depar tment of Anaesthesiology, Thessaloniki, Greece Background and Goal of Study: Propofol is an appropriate component for total intravenous neuroanesthesia but it is not the ideal agent in obese patients because of the risk of delayed awakening. In these cases sevoflurane is pref- erable, which however provoke vasodilation and impair cerebral autoregula- tion. Esmolol an ultra-shor t-acting b 1 -adrenergic receptor antagonist that is ef fective in blunting sympathetic overdrive to several perioperative stimuli, is repor ted that enhances the analgesic ef fect of opioids but has no analgesic ef fect when administered alone. This study aims to reveal the ef fect of esmo- lol on propofol consumption in patients undergoing craniotomy. Materials and Methods: Six teen patients undergoing elective craniotomy for tumor resection or aneurysm clipping were randomly divided in t wo groups of eight patients each; control and esmolol group. General anesthesia was induced with propofol (2mg/Kg), fentanyl (2mcg/Kg) and cis-atracurium (0.15mg/Kg). Anesthesia was maintained with remifentanil and propofol in 50% O 2 /N 2 O in order to maintain BIS 40-50. Patients in the esmolol group received 500mcg/Kg esmolol followed by continuous infusion of 200mcg/Kg/ min. Results and Discussion: At the esmolol group propofol was started at 50mcg/kg/min just af ter the intubation and it was adjusted perioperative ac- cording to BIS at 18-35mcg/kg/min (25.83±9.32), while at the control group was star ted at 100-150mcg/Kg/min with no significant changes in the anes- thetic requirements through the procedure. None of the patients presented any hemodynamic instabilit y due to esmolol. Conclusion(s): Intraoperatively infusion of esmolol not only managed to con- trol the sympathetic overdrive, but also diminished propofol consumption, resulting in early and smooth emergence. One explanation may be a central antinociceptive ef fect of b-adrenoceptor block. References: 1. Hans P, Bonhomme V. Why we still use intravenous drugs as the basic regimen for neurosurgical anaesthesia. Curr Opin Anesthesiol 2006;19:498-503. 2. Yang H, Fayad A. Are beta-blockers anesthestics? Can J Anaesth. 2003;50(7):627-30. 3. Taira Y, Kakinohana M, Kakinohana O, Okuda Y. ONO 1101, a novel ultra-short acting b1 blocker can reduce pain behaviour in the rat formalin test. Anesthesiology 1998; 89: A1128. 9AP7-1 Ef fect of sevoflurane on calcium homeostasis during depolarization in human skeletal myotubes Migita T., Mukaida K., Hamada H., Ichihara Y., Kikuchi H., Kawamoto M. Hiroshima Universit y Hospital, Depar tment of Anaesthesiology, Hiroshima, Japan Background and Goal of Study: Volatile anesthetics and depolarizing mus- cle blocking agents are potential triggers for Malignant Hyper thermia (MH). The goal of this study is clarif y the ef fect of sevoflurane combined with depo- larizing muscle blocking agents on calcium homeostasis in human skeletal myotubes. Materials and Methods: Four teen subjects whose skeletal muscles were bi- opsied were classified into MH-prone group (n=8) and non-MH prone group (n=6). Dif ferentiated myotubes were labeled with the calcium-sensitive probe Fura-2 AM, and the changes in the 340/380 nm ratio were used to calculate the changes in intracellular Ca 2+ concentration ([Ca 2+ ] i ) following 1 minute treatment with 1 mM sevoflurane and 60 mM KCl, that was used to depolar- ize the myotubes. Nex t, in MH prone group, similar procedure was done by removing ex tracellular Ca 2+ or adding 20 µM SKF 96365. Data are shown as mean ± SD. Unpaired t-test was used for the group com- parisons and P values less than 0.05 were considered to be statistically sig- nificant. Results and Discussion: Sevoflurane during KCl depolarization increased [Ca 2+ ] i to 166.5 ± 63.9% of sevoflurane-free condition in MH-prone group and to 103.8 ± 9.9% in non-MH prone group (P= 0.028), respectively. In MH- prone group, sevoflurane ex tended the total response time of the Ca 2+ tran- sient without any change on the peak amplitude. By removing ex tracellular Ca 2+ or adding SFK 96365 to Ca 2+ buf fer, sevoflu- rane-induced Ca 2+ transient during KCl depolarization was reduced to 37.6 ± 14.2% and 41.5 ± 16.2% of the control, respectively. Similarly, sevoflurane- induced Ca 2+ transient without KCl was reduced to 38.8 ± 18.6% and 43.3 ± 29.3% of the control, respectively. The prolonged increase in [Ca 2+ ] i was shown in existence of sevoflurane dur- ing KCl depolarization, and the response diminished in the same degree by removing ex tracellular Ca 2+ and adding SFK 96365. As SKF 96365 inhibited stromal interaction molecule 1 (STIM1)-mediated Ca 2+ influx, store-operated calcium entr y (SOCE) may contribute the increase of [Ca 2+ ] i . Conclusion(s): Clinical concentration of sevoflurane during KCl depolariza- tion prolonged increase in [Ca 2+ ] i of human skeletal muscle. The combination of sevoflurane and depolarizing muscle blocking agents may increase risk of triggering MH. References: Duke AM, Hopkins PM, Calaghan SC, et. al. J. Biol. Chem. 285: 25645-53, 2010. 9AP7-3 Mutated p.4894 RYR1 function related to malignant hyper thermia and congenital neuromuscular disease with uniform t ype 1 fiber (CNMDU1) Haraki T., Yasuda T., Mukaida K., Migita T., Hamada H., Kawamoto M. Hiroshima Universit y, Depar tment of Anaesthesiology and Intensive Care, Hiroshima, Japan Background and Goal of Study: Ryanodine receptor 1 (RYR1) is a Ca 2+ -re- lease channel located in the sarcoplasmic membrane of skeletal muscle. More than 200 mutations in RYR1 have been identified, and shown to be associated with malignant hyper thermia (MH) and congenital myopathies. The A4894T RYR1 mutation was found in a Japanese patient with susceptibilit y to MH, and the A4894P mutation in a rare case of myopathy: congenital neuromuscular disease with uniform t ype 1 fiber (CNMDU1). We hypothesized that the dif- ferent A4894 mutants of RYR1 cause dif ferent pathophysiological changes. Materials and Methods: Mutated RYR1 expression vector corresponding to A4894T or A4894P mutation was transfected into human embryonic kidney (HEK)-293 cells. At 72 hours af ter transfection, the cells were loaded with Fura-2 AM for 1 hour. Next, the cells were excited alternately at 340 and 380 nm, and the fluorescence emissions of Fura-2 were observed at 510 nm to evaluate the intracellular Ca 2+ changes. We determined the intracellular Ca 2+ changes induced by caf feine or 4-chloro-m-cresol (4CmC). Results and Discussion: Wild type (WT) and A4894T-transfected cells were sensitive to caf feine and 4CmC. The EC50 values of WT and A4894T-trans- fected cells for caf feine were 1.38 ± 0.10 (mean ± SD) and 0.52 ± 0.04 mM respectively, and for 4CmC were 176.6 ± 9.0 and 77.9 ± 8.6 mM, respec- tively. The values of A4894T were lower than that of WT (P< 0.001). These results indicate that A4894T mutant is associated with MH.On the other hand, A4894P-transfected cells were insensitive to caf feine and 4CmC. The insen- sitivity of RYR1 leads to reduction of Ca 2+ release from SR to cy toplasm and consequently causes muscle weakness, suggesting that the A4894P mutation is associated with CNMDU1. This is the first known functional analysis of the RYR1 mutation in CNMDU1. Conclusion(s): We concluded that dif ferent A4894 mutants of RYR1 lead to dif ferent functions of RYR1, and the A4894T mutation in RYR1 is associated with MH and the A4894P with CNMDU1. Acknowledgements: We appreciate Professor David H. MacLennan for the generous gif t of Rabbit-RYR1/pc DNA. 9AP7-4 Mannitol: A sur vey of its practice in par tial and live donor nephrectomy Sabaté S., Breda A., Vernetta D., Alvarez A., Hernando S. Fundació Puigver t (IUNA), Depar tment of Anaesthesiology, Barcelona, Spain Background and Goal of Study: Mannitol is frequently used as a kidney pro- tector during warm ischemia time during par tial and live donor nephrectomy