Objective To explore the ideal speed for the infusion of loading dose of dexmedetomidine in patients with hypertension.Methods One hundred and twenty patients with essential hypertension were selected,and they were randomly divided into A,B,C,D four groups according to the digital table,30 cases in each group.All patients were administered the same loading dose(1.0μg/kg) of dexmedetomidine according to the total body weight,the pump infusion time in the four groups was 10,15,20 or 25min,respectively.The mean arterial pressure (MAP) and heart rate(HR) were observed before infusion(T0) and 5 min (T1),10 min (T2),15 min (T3),20 min (T4),25 min(T5),30 min(T6),35 min(T7) after administration.Results Compared with before injection,A group had an increase of MAP[(116.0± 3.4)mmHg] at the point of T3 (t =17.32,P =0.001),B group had an increase of MAP [(115.0 ± 3.3) mmHg] at the point of T3 (t =16.21,P =0.003),C group and D group had no increase of MAP at the point of T0 ～ T7.Conclusion Loading dose (t.0 μ.g/kg) of dexmedetomidine should be pumped in more than 20 min in patients with primary hypertension to maintain steady blood pressure.

Objective To investigate the neurotoxicity of intrathecal (IT) doxepin in rats.Methods Twenty-four adult male Wistar rats weighing 250-300 g in which intrathecal micro-catheter was successfully implanted without complications were randomly divided into 4 groups ( n =6 each):control group ( group N ) and 3 doxepin groups receiving IT doxepin 40,20 and 10 mmol/L 0.2 μl/g respectively (groups D40,D20,D10 ).In N group normal saline was injected IT instead of doxepin.The animals were killed at 6 h after IT administration.The lumbar segment of the spinal cord was removed for microscopic examination and determination of myelin basic protein (MBP) content in the spinal cord using a double-antibody sandwich (ELISA).Results The severity of neuronal damage and decrease in MBP content in the spinal cord induced by IT doxepin were dose-dependent.Conclusion The neurotoxicity induced by IT doxepin is dose-dependent.

Objective To evaluate the effect of rocuronium on entropy to endotracheal intubation during anesthesia induction with propofol. Methods Forty patients anesthetized induction with propofol using a target-controlled infusion were randomly divided into two groups: rocuronium group (R group, 20 cases) received 0.6 mg/kg rocuronium or saline group (S group, 20 cases) received saline. 2-3 min later, endotracheal intubation was performed. Response entropy(RE) and state entropy(SE) were recorded during baseline(Ta), at steady state(Tb), 2 min after rocuro nium or saline administration (Tc) and 0, 1, 2 and 3 min after endotracheal intubation (T0, T1, T2, T3). Results At T2, the RE-SE was higher in S group than that in R group. Endotracheal intubation induced increasing in RE and SE. Comparing T2 and T0 values in R group and S group, SE increased from 42 ± 7 to 50 ± 8 and 43 ± 13 to 55 ± 12, and RE increased from 45 ± 6 to 54 ± 9 and 48 ± 16 to 66 ± 15, respectively. At T0, RE and RE-SE were higher in S group. Conclusion Rocuronium affects RE-SE and RE and RE-SE responses to endotracheal intubation and may confound interpretation of entropy monitoring.

Objective To investigate the role of mitochondrial apoptotic pathway in intrathecal doxepin?induced apoptosis in rat neurons. Methods Twenty?four adult male Wistar rats, weighing 250-300 g, in which intrathecal catheters were successfully implanted without complications, were randomly divided into 4 groups ( n=6 each) using a random number table: control group ( group C) and different concentrations of doxepin groups (D5, D10 and D20 groups). In D5, D10 and D20 groups, 5, 10, and 20 mmol∕L doxepin 0. 2 μl∕g were injected intrathecally, respectively. In group C, the equal volume of normal saline was given instead. At 6 h after intrathecal administration, the animals were sacrificed, and the lumbar segments of the spinal cords were obtained for detection of the cell apoptosis ( by TUNEL assay) , expression of Bax and Bcl?2 ( by immunohistochemistry) , release of cytochrome c ( Cyt c) , and expression of caspase?3, caspase?8 and caspase?9 mRNA ( using real?time reverse transcriptase polymerase chain reaction) . Apoptosis rate and Bcl?2∕Bax ratio were calculated. Results Compared with group C, the expression of Bax was significantly up?regulated, the expression of Bcl?2 was down?regulated, Bcl?2∕Bax ratio was decreased, the release of Cyt c and apoptosis rate were increased, and the expression of caspase?3 and caspase?9 mRNA was up?regulated in D10 and D20 groups, the expression of Bcl?2 was down?regulated in group D20 ( P<0.05 or 0.01) , and no significant change was found in the parameters mentioned above in group D5 (P>0.05). The expression of Bax was significantly up?regulated, Bcl?2∕Bax ratio was decreased, the release of Cyt c and apoptosis rate were increased, and the expression of caspase?3 and caspase?9 mRNA was up?regulated in D10 and D20 groups, and the expression of Bcl?2 was down?regulated in group D20 as compared with group D5 ( P<0.05 or 0.01) , and in group D20 as compared with group D10 ( P<0.05) . There was no significant difference in the expression of caspase?8 mRNA among the four groups ( P>0.05) . Conclusion Mitochondrial apoptotic pathways, but not death receptor pathway, is involved in intrathecal doxepin?induced apoptosis in rat neurons.

Objective To investigate the effect of caspases-3 on doxepin-induced apoptosis in rat neurons.Methods The PC12 cells seeded in culture plates were randomly divided into 4 groups (n =10 each) using a random number table:normal control group (group C);doxepin group (group D);caspase-3 inhibitor Z-DEVD-FMK group (group Z);doxepin + Z-DEVD-FMK group (group DZ).In group C,the cells were continuously incubated for 24 h.In group D,doxepin was added with the final concentration of 120 μmol/L,and the cells were continuously incubated for 24 h.In group Z,Z-DEVD-FMK was added with the final concentration of 10 μmol/L,and the cells were continuously incubated for 24 h.In group DZ,doxepin and Z-DEVD-FMK with the final concentrations of 120 and 10 μmol/L,respectively,were added,and the cells were continuously incubated for 24 h.After 24 h of incubation,the cell viability was detected by methyl thiazolyl tetrazolium assay,the cell morphology was observed under inverted microscope,and the neuronal apoptosis was measured by flow cytometry.Apoptosis rate was calculated.Results Compared with group C,the cell viability was significantly decreased,and apoptosis rate was increased in D and DZ groups (P＜0.01),and no significant change was found in the parameters mentioned above in group Z (P ＞ 0.05).Compared with group D,the cell viability was significantly increased,and apoptosis rate was decreased in group DZ (P＜ 0.01).The morphological changes were significantly mitigated in group DZ as compared with group D.Conclusion Caspases-3 may mediate doxepin-induced apoptosis in rat neurons.

Objective To evaluate the effect of dexmedetomidine on cell apoptosis during spinal cord ischemia-reperfusion(I∕R)in rats. Methods Forty-eight adult male Wister rats, weighing 200-260 g, were divided into 4 groups(n=12 each)using a random number table: sham operation group (Sham group), I∕R group, prophylactic dexmedetomidine use group(DPro group)and dexmedetomidine postconditioning group(DPost group). The model of spinal cord I∕R was established by temporary occlu-sion of the abdominal aorta using the modified Zivin′s method. Dexmedetomidine 5 μg·kg-1·h-1was in-travenously infused at 1 h before occlusion of the abdominal aorta in group DPro. Dexmedetomidine 5 μg·kg-1·h-1was intravenously infused for 1 h starting from the time point immediately after beginning of reperfusion in group DPost. The equal volume of normal saline was given instead in Sham and I∕R groups. The motor nerve function of the hindlimb was assessed and scored at 4, 12 and 24 h of reperfusion. The rats were sacrificed at 24 h of reperfusion, and L2-5segments of the spinal cords were removed for microscopic examination and for determination of Bcl-2 and Bax positive cells(by immuno-histochemistry)and cell ap-optosis(by flow cytometry). The apoptosis rate was calculated. Results Compared with group Sham, motor nerve function scores were significantly decreased at 4-12 h of reperfusion, and the apoptosis rate of nerve cells and Bcl-2 and Bax positive cells were increased in group I∕R, and motor nerve function scores were significantly decreased at 4 h of reperfusion, and the apoptosis rate of nerve cells and Bcl-2 and Bax positive cells were increased in DPro and DPost groups(P<005 or 001). Motor nerve function scores were significantly higher, and the apoptosis rate of nerve cells was lower, Bcl-2 positive cells were higher, and Bcl-2 and Bax positive cells were lower in DPro and DPost groups than in group I∕R(P<005 or 001). Conclusion The mechanism by which dexmedetomidine reduces spinal cord I∕R injury is related to inhibiting cell apoptosis in rats.

Objective To evaluate the effect of doxepin on the expression of p38 mitogen-activated protein kinase (p38 MAPK) in the spinal cord of rats with neuropathic pain (NP).Methods Sixty clean-grade male Wistar rats in which intrathecal catheters were successfully implanted,weighing 200-250 g,were divided into 3 groups (n =20 each) by a random number table method:sham operation group (S group),NP group and doxepin group (D group).NP was induced by chronic constriction injury (CCI) to sciatic nerve.Doxepin 20 mmol/L (10 μl) was intrathecally injected at 3,7,14 and 21 days after CCI (T1-4) in group D.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before CCI (T0) and at T1-4.The rats were sacrificed after measurement of pain threshold at T4,and L4-6 segments of the spinal cord were removed for determination of the expression of p38MAPK protein by Western blot.Results Compared with S group,MWT was significantly decreased and TWL was shortened at T2-4,and the expression of p38MAPK protein was up-regulated in NP and D groups (P＜0.05).Compared with NP group,MWT was significantly increased and TWL was prolonged at T2-4,and the expression of p38MAPK protein was down-regulated in D group (P＜0.05).Conclusion The mechanism by which doxepin mitigates NP is related to down-regulating p38MAPK expression in the spinal cord of rats.