ObjectiveTo investigate the effect of dexmedetomidine postconditioning on mitochondria injury during myocardial ischemia-reperfusion (I/R) in isolated rat hearts.Methods Healthy female Wistar rats weighing 220-250 g were anesthetized with intraperitoneal 3％ pentobarbital 50 mg/kg and heparin 500 U/kg.Their hearts were excised and perfused in a Langenorff apparatus with modified K-H solution saturated with 95％ O2-5％ C02 at 37 ℃.Forty isolated rat hearts were randomly divided into 5 groups( n =8 each): I/R group(group A),dexmedetomidine 10 nmol/L group ( group B),dexmedetomidine 100 nmol/L group ( group C ),atractyloside ( the mitochondrial permeability transitionpore (mPTP) opener) group (group D)and dexmedetomidine 100 nmol/L + atractyloside group(group E).Myocardial I/R injury was induced by 40 min of global ischemia followed by 60 min of reperfusion.10 nmol/L dexmedetonidine( group B),100 nmol/L dexmedetonidine (group C),20 μmol/L atractyloside(group D) or 100 nmol/L dexmedetomidine + 20 μmol/L atractyloside (group E) was added into K-H solution and perfused for 10 min at the beginning of reperfusion.The myocardial tissues were obtained and mitochondria were isolated at the end of reperfusion for determination of activity of SOD,Na+ -K+ -ATPase,and Ca2+ -ATPase and content of MDA and Ca2+.ResultsThe activity of SOD,Na+ -K+ -ATPase and Ca2+ -ATPase was significantly higher and MDA and Ca2+ content lower in groups B and C than in group A( P ＜ 0.05).The activity of SOD,Na+ -K+ -ATPase and Ca2+ -ATPase was lower and MDA and Ca2+ content higher in groups E and D than in group C (P ＜ 0.05).There was no significant difference in activity of SOD,Na+ -K+ -ATPase and Ca2+ -ATPase and MDA and Ca2+ content between groups B and C,and between groups A and D( P ＞ 0.05).Conclusion Dexmedetomidine postconditioning can reduced mitochondria injury during myocardial I/R in isolated rat hearts through inhibiting of mPTP opening.

ObjectiveTo investigate the effects of sevoflurane preconditioning on myocardial connexin 43 (Cx43) during myocardial ischemia-reperfusion (I/R) in rats.MethodsMale adult Wistar rats weighing 220-250 g were anesthetized with intraperitoneal pentobarbital 40 mg/kg and heparin 500 IU/kg.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 37 ℃ for 30 min.Sixteen isolated rat hearts were randomly assigned into 2 groups ( n =8 each):I/R group and sevoflurane preconditioning group (group SP).At 30 min of equilibration,group I/R received perfusion for another 20 min,the hearts were purfused with K-H solution saturated with 2.4％ sevoflurane for 15 min followed by 5 min washout with K-H solution in group SP.Then all the hearts underwent 40 min of ischemia followed by 60 min of reperfusion.HR,left ventricular developed pressure (LVDP),+ dp/dtmax and - dp/dtmax were recorded at the end of equilibration,immediately before ischemia and at 30 and 60 min of reperfusion.Myocardial tissues were obtained from apex for microscopic examination and from left ventricle for observation of distribution of Cx43 and determination of Cx43 expression.ResultsCompared with the baseline value at the end of equilibration, + dp/dtmax and - dp/dtmax immediately before ischemia and HR,LVDP,+ dp/dtmax and - dp/dtmax at 30 and 60 min of reperfusion were significantlydecreased in groups I/R and SP (P ＜ 0.01 ).Compared with that immediately before ischemia,HR,LVDP, + dp/dtmax and - dp/dtmax were significantly decreased at 30 and 60 min of reperfusion in groups I/R and SP (P ＜ 0.05 or 0.01).Compared with group I/R,HR,LVDP,+ dp/dtmax and - dp/dtmax were significantly decreased immediately before ischemia,HR,LVDP, + dp/dtmax and - dp/dtmax were significantly increased at 30 and 60 min of reperfusion ( P ＜ 0.01 ),and pathological injury was attenuated in group I/R.Myocardial Cx43 was unevenly distributed in group I/R,while evenly distributed in group SP.There was no significant difference in Cx43 expression between the two groups.ConclusionThe mechanism by which sevoflurane preconditioning protects myocardium against I/R injury may be related to redistribution of Cx43,but not Cx43 expression.

Objective To investigate the effects of different doses of penehyclidine hydrochloride on postoperative cognitive function in the elderly patients.Methods Ninety-three ASA Ⅰ or Ⅱ elderly patients,aged ≥65 yr,weighing 55-71 kg,were randomly divided into 3 groups (n =31 each):penehyclidine hydrochloride 0.010 mg/kg group (group A),penehyclidine hydrochloride 0.015 mg/kg group (group B) and atropine 0.010 mg/kg group (group C).Their preoperative Mini-Mental State examination (MMSE) scores were ＞ 27.At 30 min before anesthesia,groups A,B and C received intramuscular penehyclidine hydrochloride 0.010 mg/kg,penehyclidine hydrochloride 0.015 mg/kg and atropine 0.010 mg/kg,respectively.The cognitive function of the patients was assessed within 72 h after operation using MMSE.Diagnostic criterion of postoperative cognitive dysfunction (POCD) was defined as MMSE score ≤27.POCD and the degree were recorded within 72 h after operation.Results Compared with group A,postoperative cognitive function was significantly decreased at each time point after operation and the incidence of POCD was significantly increased in group B (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group C (P ＞ 0.05).Compared with group B,postoperative cognitive function was significantly enhanced at each time point after operation and the incidence of POCD was significantly decreased in group C (P ＜ 0.05).Conclusion Penehyclidine hydrochloride can depress postoperative cognitive function and the effect is related to the dose.

Objective To investigate the effect of sevoflurane preconditioning combined with postconditioning (Spost) on anoxia/reoxygenation (A/R) injury to neonatal rat cardiomyocytes.Methods Primary cultured neonatal rat cardiomyocytes were isolated from SD rats aged 1-3 days and cultured in DMEM liquid culture medium.The cells were seeded in 24-well plates (1 ml/hole),35 mm diameter dishes (5 ml/dish) or in 50 mm culture flasks (8 ml/flask) with a density of 3 × 105/ml and randomly divided into 9 groups (n =24 each):control group (group C),A/R group,Spre group (group S1),Spre + SB203580 group (group S1 + SB),sevoflurane postcon-ditioning (Spost) group (group S2),Spost + SB203580 group(group S2 + SB),Spre + Spost group (group S3),Spre + Spost + SB203580 group (group S3 + SB),and group SB203580 (group SB).The cells were cultured routinely for 160 min in group C and the cells were exposed to 95％ N2-5％ CO2 in an incubator at 37 ℃ for 120 min followed by reoxygenation for 20 min in the other groups.The cells were incubated with 2.5 ％ sevoflurane for 20 min before anoxia in groups S1,S1 + SB,S3 and S3 + SB and in addition SB203580 (specific p38MAPK inhibitor) 5 μmol/L was added simultaneously in groups S1 + SB and S3 + SB.The cells were incubated with 2.5％ sevoflurane for 20 min after beginning of reoxygenation in groups S2,S2-SB,S3 and S3 + SB,and in addition SB203580 5 μmol/L was added simultaneously in groups S2 + SB and S3 + SB.The cells were incubated with SB203580 5 μmol/L for 20 min before anoxia and after beginning of reoxygenation in group SB.The lactate dehydrogenase (LDH) activity,cell survival rate and apoptotic rate were measured at the end of reoxygenation.The levels of phosphor-p38MAPK (p-p38MAPK) was detected at the end of Spre and Spost.Results Compared with group C,the LDH activity and apoptotic rate were significantly increased,while the cell survival rate was significantly decreased in the other groups (P ＜ 0.05).Compared with group A/R,the LDH activity and apoptotic rate were significantly decreased,while the cell survival rate was significantly increased in groups S1,S2 and S3 (P ＜ 0.05).There was no significant difference in the LDH activity,cell survival rate and apoptotic rate between groups S1,S2and S3 (P ＞ 0.05).The myocardial protective effect of Spre or Spost alone or in combination was eliminated by SB203580 (P ＜ 0.05).Spre or Spost alone up-regulated the expression of p-p38MAPK,Spre combined with Spost offered no additional benefit over Spre or Spost alone,and the up-regulative effect was eliminated by SB203580 (P ＜ 0.05).Conclusion Spre combined with Spost produces similar myocardial protective effect with that of either alone and it may because that both Spre and Spost attenuate A/R-induced injury to cardiomyocytes through p38MAPK signaling pathway.

Objective To investigate the volume kinetics of 6% hydroxyethyl starch 130/0.4 in healthy volunteers.Methods Seven healthy volunteers aged 18-32 yr weighing 46-84 kg were selected in this study. 6% hydroxyethyl starch 130/0.4 30 ml/kg was infused over 60 min. Volume kinetics analysis of 6% hydroxyethyl starch 130/0.4 was performed with Matlab 6.0 software, compartment model was determined by F test.Results One-compartment model parameters: basic clearance, clearance and distribution volume of one-compartment model were (3.5 ± 1.3) ml/min,(19± 11) ml/min and (5746 ± 1371) ml respectively. Two-compartment model parameters: clearance, K1, the volume of central compartment, the volume of peripheral compartment, distribution volume of two-compartment model were (63 ±29) ml/min,(11 ±4) ml/min, (1551 ± 995) ml, (908 ±398) ml,(2460 ± 1332) ml respectively. There was no difference between the distribution volume of one-compartment model and blood volume of healthy volunteers ( P ＞ 0.05) .The distribution of infused 6% hydroxyethyl starch 130/0.4 was accordant with one-compartment model (F value was 3.81, P ＞ 0.05)and 4 h clearance was (75 ± 10)% .Conclusion The distribution of infused 6% hydroxyethyl starch 130/0.4 for volume expansion is accordant with one-compartment model, and the effective duration of plasma volume expansion is 4 h.

Objective To investigate the effect of sevoflurane preconditioning on CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) expression in the cerebral cortex after focal cerebral ischemiareperfusion (I/R) injury in rats and the mechanism. Methods Thirty-six male SD rats weighing 250-280 g were randomly divided into 3 groups ( n = 12 each) : sham operation group (group S) , focal cerebral I/R group (group I/R) and sevoflurane preconditioning group (group Sevo-pc). The animals were anesthetized with intraperitoneal chloral hydrate 300 mg/kg. In groups I/R and Sevo-pc, focal cerebral ischemia was induced by middle cerebral artery occlusion using a nylon thread with rounded tip inserted into the right internal carotid artery and advanced cranially until resistance was met. The occlusion was maintained for 1 h followed by 24 h reperfusion. Group Sevo-pc inhaled 2.7% sevoflurane for 1 h before ischemia. Neurological deficits were assessed and scored at the end of 24 h reperfusion and then the rats were decapitated. Their brains were immediately removed. The cerebral infarct size was determined by TTC staining. The CHOP expression in the ischemic cerebral cortex was determined by immunohistochemistry. The number of apoptotic neurons was counted using TUNEL. Results The neurological deficit scores were significantly higher, the cerebral infarct size was significantly larger, and the CHOP expression and the number of apoptotic neurons were significantly higher in groups I/R and Sevo-pc than in group S ( P ＜ 0.01) . The neurological deficit scores were significantly lower, the cerebral infarct size was significantly smaller, and the CHOP expression and the number of apoptosis neurons were significantly lower in group Sevo-pc than in group I/R ( P ＜ 0.05 or 0.01) . Conclusion Sevoflurane preconditioning may protect the brain against focal cerebral I/R injury by down-regulating CHOP expression in the cerebral cortex in rats.

ObjectiveTo investigate the effect of dexmedetomidine pretreatment on focal cerebral ischemia-reperfusion(I/R) injury in rats.MethodsOne hundred male SD rats weighing 290-310 g were randomly divided into 5 groups(n =20 each):sham operation group(group SH) ; focal cerebral I/R group; focal cerebral I/R + dexmedetomidine 100 μg/kg(group L); focal cerebral I/R+ dexmedetomidine 200 μg/kg (group M) and focal cerebral I/R + dexmedetomidine 400 μg/kg(group H).Focal cerebral I/R was produced by occlusion of middle cerebral artery for 60 min followed by 24 h of reperfusion.Dexmedetomidine 100,200 and 400 μg/kg were injected intraperitoneally 15 min before ischemia in groups L,M and H respectively.While equal volume of normal saline was injected intraperitoneally in group SH.Neurologic function was assessed and scored at 24 h of reperfusion.Then the animals were sacrificed and brains were removed for determination of cerebral infarct volume and microscopic examination.The expression of heat shock protein 70(HSP70) and activity of Na+ -K + -ATPase in ischemic cortex and activity of SOD and concentration of cortisol in plasma were determinationed at 24 h of reperfusion.ResultsCompared with group SH,neurologic deficit scores and plasma concentration of cortisol were significantly increased,activities of SOD and Na+ -K+ -ATPase decreased and expression of HSP70 was up-regulated in groups I/R,L,M and H( P ＜ 0.05).Compared with group I/R,neurologic deficit scores and plasma concentration of cortisol were significantly decreased,activities of SOD and Na+ -K+ -ATPase increased and expression of HSP70 was up-regulated in a dose-dependent manner ( P ＜ 0.05),and the pathological change was reduced in a dose-dependent manner in groups L,M and H.ConclusionDexmedetomidine pretreatment can attenuate focal cerebral I/R injury in a dose-dependent manner through improvement of brain cell energy metabolism and reduction of lipid peroxidation and stress reaction.

Objective To investigate the effect of sevoflurane post-conditioning on the expression of poly (ADP-ribose) polymerase (PARP) in the cerebral cortex during focal cerebral ischemia/reperfusion (I/R) in rats and the mechanism.Methods Fifty-four male Sprague-Dawley rats,weighing 250-320 g,were randomly divided into3 groups (n =18 each) using a random number table:sham operation group (S group),I/R group and sevoflurane post-conditioning group (Sevo-pc group).The animals were anesthetized with intraperitoneal chloralhydrate 300 mg/kg.In Sevo-pc and I/R groups,focal cerebral ischemia was induced by middle cerebral artery occlusion using a nylon thread with rounded tip inserted into the right internal carotid artery and advanced cranially until resistance was met.The occlusion was maintained 1 h,followed by 24 h reperfusion.The animals in Sevo-pc group inhaled 2.7％ sevoflurane for 1 h starting from onset of reperfusion.At 24 h of reperfusion,neurological deficits were assessed,and then the rats were decapitated.The brains were immediately harvested for determination of the cerebral infarct size (by TTC staining) and expression of PARP in the ischemic cerebral cortex (by immunohistochemistry).The number of apoptotic cells was counted using TUNEL.The apoptosis index was calculated.Results Compared with group S,the neurological deficit scores and apoptotic cells were significantly increased,the cerebral infarct size was enlarged,and the expression of PARP in the ischemic cerebral cortex was up-regulated in I/R and Sevo-pc groups (P ＜ 0.05 or 0.01).The neurological deficit scores and apoptotic cells were significantly lower,the cerebral infarct size was smaller,and the expression of PARP in the ischemic cerebral cortex was downregulated in Sevo-pc group (P ＜ O.05 or 0.01).Conclusion Sevoflurane post-conditioning can reduce focal cerebral I/R injury in rats and down-regulation of PARP expression in the cerebral cortex may be involved in the mechanism.

Objective To investigate the effect of butylphthalide and sodium chloride injection postconditioning on focal cerebral ischemia-reperfusion (I/R) injury and endoplasmic reticulum stress in rats.Methods Thirty-six male SPF Sprague-Dawley rats,aged 2-3 months,weighing 260-280 g,were randomly divided into 3 groups (n =12 each):sham operation group (group S),focal cerebral I/R group (group I/R) and butylphthalide and sodium chloride injection postconditioning group (group Buty).The animals were anesthetized with intraperitoneal 10 ％ chloral hydrate 300 mg/kg.Focal cerebral I/R was induced by occluding right middle cerebral artery for 2 h followed by 24 h reperfusion in I/R and Buty groups.Butylphthalide and sodium chloride injection 2.5 mg/kg was injected via the tail vein immediately after onset of reperfusion in Buty group,while the equal volume of normal saline was injected in I/R group.Neurological deficits were assessed and scored at 24 h of reperfusion,and then the brain was isolated for detection of neuronal apoptosis (by TUNEL) and the expression of glucose-regulated protein 78 (GRP78) and caspase-12 in ischemic cerebral cortex (by immunohistochemistry) in brain tissues.Apoptosis index was calculated.Results Compared with group S,the neurological deficit scores and apoptosis index were significantly increased,and the expression of GRP78 and caspase-12 was up-regulated in I/R and Buty groups (P ＜ 0.05 or 0.01).Compared with group I/R,the neurological deficit scores and apoptosis index were significantly decreased,the expression of GRP78 was up-regulated,and the expression of caspase-12 was down-regulated in group Buty (P ＜ 0.05).Conclusion Butylphthalide and sodium chloride injection postconditioning can reduce focal cerebral I/R injury in rats,and inhibition of endoplasmic reticulum stressmediated cell apoptosis is involved in the mechanism.

Objective To determine the effective volume of 1.5％ lidocaine for obturator nerve block (ONB) in 50％ of patients (EV50) undergoing transurethral resection of bladder tumor (TURBT).Methods Thirty-six ASA physical status Ⅰ or Ⅱ patients with bladder tumor,aged 18-64 yr,with body mass index of 19-30 kg/m2,scheduled for elective TURBT and required ONB before TURBT,were enrolled in the study.ONB was performed with 1.5 ％ lidocaine using the pubic approach under the guidance of a nerve stimulator.The volume of 1.5％ lidocaine was determined by up-and-down sequential trial.The initial volume of hdocaine was 10 ml and the ratio between the two successive volumes was 1.1.Successful ONB was considered to be positive response.The EV50 and 95 ％ confidence interval (CI) of 1.5 ％ lidocaine for ONB were calculated.Results The EV50 of 1.5 ％ lidocaine for ONB was 5.53 rnl and the 95 ％ CI was 5.10-6.00 ml.Conclusion The EV50 of 1.5 ％ lidocaine is 5.53 ml when used for ONB in patients undergoing TURBT.