Objective To investigate the effects of nicorandil (Nic) pretreatment on myocardial apoptosis in a rabbit model of myocardial ischemia/reperfusion (I/R) .Methods Forty healthy male New Zealand white rabbits aged 4 months weighing 2.0-2.5 kg were randomly allocated to one of 5 groups ( n = 8 each); group 1 sham operation; group 2 I/R; group 3 Nic; group 4 Nic + 5-hydroxydecanoic acid (5-HD) and group 5 Nic + glibenclamide (Gli) . The animals were anesthetized with IV pentobarbital 30 mg?kg-1 and tracheotomized and breathing spontaneously. A piece of thread was placed around the circumflex branch of left coronary artery, which was reversibly occluded for 30 min and released for 120 min reperfusion. In group 3, 4 and 5 a loading dose of 100 ?g?kg-1 Nic was given IV 10 min before myocardial ischemia followed by Nic infusion at 10 ?g?kg-1 ?min-1 until myocardial ischemia was started. In group 4 and S 5-HD 5 mg? kg-1 or Gli 5 mg? kg-1 was given IV 20 min before ischemia. At the end of 120 min reperfusion the animals were killed and the hearts removed. The area of myocardial infarct (AI), and the ischemic risk zone (AR) were determined by computer morphometry. The early apoptotic myocytes were detected by flow cytometry (Beckman, Coulter Co). The expression of caspase-3 protein was determined by immuno-histochemistry. The myocardial ultrastructure was examined with transmission electron microscope.Results Compared to group 2 (I/R) , in nicorandil group (group 3) the size of myocardial infarct and the number of early apoptotic cells were significantly reduced, the ultrastructure of myocardium was well-preserved and the expression of activated caspase-3 protein decreased. The protective effect of Nic preconditioning was greatly inhibited by 5-HD and Gli pretreatment. Conclusion Nicorandil pretreatment exerts protective effect against myocardial I/R injury through activation of mito-KATP C and inhibition of activation of caspase-3.

Objective To investigate the influences of hypothermia on hemodynamics and hemorrheology .Methods The body temperature of 10 mongrel dogs decreased at 35℃ ,and was kept for 30 min, and then warmed to normal degree with physical methods. The parameters of hemodynamics and hemorrheology were measured with the polygraph system (RM 6000, Nihon Kohden).Results Compared with the baselines, 30 min following hypothermia heart rate, mean arterial pressure, cardiac output, maximum rate of rise and decline of pressure(?dp/dtmax),cardiac index, left ventricular stroke work index were significantly reduced, while systemic peripheral resistance , blood viscosity were higher than those under normal body temperature (P

Objective To evaluate the effects of different doses of fentanyl on the median effective target plasma concentration (EC50) of propofol inhibiting body movement evoked by gastroscopy in the elderly patients.Methods Ninety patients of both sexes,aged 75-89 yr,with a body mass index of 19-25 kg/m2,of ASA physical status Ⅱ or Ⅲ,scheduled for elective gastroscopy,were randomly divided into 3 groups (n =30 each):control group (group C) and different doses of fentanyl groups (F0.5 and F1.0 groups).Fentanyl 0.5 and 1.0 μg/kg were injected intravenously in F0.5 and F1.0 groups,respectively.Propofol was then administered by target-controlled infusion.The initial target plasma concentrations (Cps) of propofol were 2.0,1.5 and 1.0 μg/ml in C,F0.5 and F1.0 groups,respectively.Gastroscopy was performed after the target effect-site and plasma concentrations were balanced.Body movement was defined as movement in head or four extremities during gastroscopy.The target Cp of propofol was determined by up-and-down sequential trial.Each time the Cp increased/decreased by 0.5 μg/ml in the next patient depending on whether or not body movement developed.The EC50 and 95 ％ confidence interval (CI) of propofol inhibiting gastroscopy-evoked body movement were determined using Probit analysis.Results The EC50 (95 ％ CI) of propofol was 2.24 ng/ml (1.67-2.47 ng/ml) in group C,1.79 (1.55-1.95) μg/ml in group F0.5,and 1.13 (1.08-1.62) μg/ml in group F1.0.There was no significant difference in the EC50 of propofol between F0.5 and C groups.The EC50 of propofol was significantly lower in F1.0 group than in C and F0.5 groups.Conclusion When combined with propofol,fentanyl 1.0 μg/kg is recommended for gastroscopy in the elderly patients.

Objective To evaluate the effect of age on the median-effective target plasma concentration (EC50) of propofol inhibiting body movement evoked by gastroscopy in the patients.Methods Ninety adult patients of both sexes,of ASA physical status Ⅰ or Ⅱ,with body mass index 19-25 kg/m2,scheduled for elective gastroscopy,were divided into 3 groups according to age (n =30 each):18-39 yr group (Ⅰ group),40-64 yr group (Ⅱ group) and 65-85 yr group (Ⅲ group).In Ⅰ,Ⅱ,Ⅲ groups,propofol was given by target-controlled infusion with the initial target concentrations of 2.5,2.0 and 1.5 μg/ml,respectively,and gastroscopy was performed when the target concentration was achieved.Body movement was defined as the directional movement in head or four extremities during gastroscopy.The target plasma concentration of propofol was determined by up-and-down sequential trial.Each time the plasma concentration of propofol increased/decreased by 0.5 μg/ml in the next patient depending on whether or not body movement developed.The EC50 and 95 ％ confidence interval of propofol inhibiting gastroscopy-evoked body movement were determined using Probit analysis.Results The EC50 (95 ％ confidence interval) of propofol was 4.2(3.8-4.5),4.1(3.7-4.4) and 2.4(1.8-2.7) μg/ml in Ⅰ,Ⅱ and Ⅲ groups,respectively.There was no significant difference in the EC50 of propofol between group Ⅱ and group Ⅰ.The EC50 of propofol was significantly lower in group Ⅲ than in Ⅰ and Ⅱ groups.Conclusion Age affects propofol-induced analgesia in patients with visceral pain,and the potency of propofol inhibiting visceral pain during gastroscopy in the elderly patients is significantly enhanced as compared with that in the young and middle-aged patients.

Objective To evaluate the role of Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling pathway in propofol-induced neuroapoptosis in the hippocampus of newborn rats.Methods Experiment Ⅰ Primarily cultured hippocampal neurons were seeded in 6-well culture plates at a density of 1×106 cells/ml and divided into 2 groups (n=6 each) using a random number table:solvent control group (C group) and propofol group (P group).Propofol was added with the final concentration of 60 μg/ml in group P.Dimethyl sulfoxide was added with the final concentration of 0.04％ in group C.The expression of RhoA and ROCK2 in hippocampal neurons was measured by Western blot at 24 h of incubation.Experiment Ⅱ Primarily cultured hippocampal neurons were seeded in 6-well culture plates at a density of 1 × 106 cells/ml and divided into 3 groups (n =6 each) using a random number table:solvent control group (C group),propofol group (P group) and propofol plus specific RhoA/ROCK2 signaling pathway blocker Y27632 group (P+Y group).Propofol was added with the final concentration of 60 μg/ml in group P.Propofol at the final concentration of 60 μg/ml and Y27632 at the final concentration of 10 μmol/L were added in group P+Y.Dimethyl sulfoxide was added with the final concentrauon of 0.04％ in group C.At 24 h of incubation,the neuroapoptosis in hippocampi was detected by flow cytometry,and the expression of activated caspase-3 in hippocampal neurons was measured by Western blot.The apoptotic rate was calculated.Results Experiment Ⅰ Compared with group C,the expression of RhoA and ROCK2 in hippocampal neurons was significantly up-regulated in group P (P＜0.05).Experiment Ⅱ Compared with group C,the apoptotic rate of hippocampal neurons was significantly increased,and the expression of activated caspase-3 was up-regulated in P and P+Y groups (P＜0.05 or 0.01).Compared with group P,the apoptotic rate of hippocampal neurons was significantly decreased,and the expression of activated caspase-3 was down-rcgulatcd in group P + Y (P＜ 0.05).Conclusion Activation of RhoA/ROCK2 signaling pathway is involved in propofol-induced neuroapoptosis in hippocampi of newborn rats.

Objective To evaluate the role of conventional protein kinase Cγ (cPKCγ)/growthassociated protein-43 (GAP-43) signaling pathway in ketamine-induced apoptosis in hippocampal neurons of developing rats in an in vitro experiment.Methods Primarily cultured hippocampal neurons were seeded in culture plates at a density of 1×10.6 cells/ml and divided into 2 groups (n=10 each) using a random number table:control group (C group) and ketamine group (K group).Group C received no treatment.Ketamine was added with the final concentration of 300 μmol/L in group K.At 12 h of culture or incubation,the apoptosis in hippocampal neurons was detected by flow cytometry.The apoptotic rate was calculated.The expression of cPKCγ,GAP-43 and phosphorylated GAP-43 in hippocampal neurons was measured by Western blot.Results Compared with group C,the apoptotic rates of hippocampal neurons were significantly increased,and the expression of cPKCγ,GAP-43 and phosphorylated GAP-43 was down-regulated in group K (P<0.01).Conclusion The mechanism by which ketamine induces apoptosis in hippocampal neurons of developing rats may be related to inhibition of cPKCγ/GAP-43 signaling pathway activation in an in vitro experiment.