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Objective To evaluate the effect of sevoflurane on memory retrieval in mice and the role of hippocampal PSD95 and amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor.Methods Sixty-four healthy pathogen-free Kuming mice of both sexes,aged 2-3 months,weighing 30-35 g,were divided into control group (n =32) and sevoflurane group (n =32) in a stratified randomized block design.The ability of memory retrieval was evaluated using dark avoidance test.After setting up the memory of dark avoidance,the mice inhaled 40％ oxygen for 2 h in control group and 3.3％ sevofluane in 40％ oxygen for 2 h in sevoflurane group.Dark avoidance test was performed at 12,24,48 and 72 h after the end of oxygen or sevoflurane inhalation (T1-4),and the test results and development of amnesia were recorded.The animals were sacrificed after behavior test at each time point,and brains were removed and cut into sections which were stained with haematoxylin and eosin for examination of the pathological changes of hippocampal CA1 area (under a light microscope) and for determination of the expression of PSD95 and AMPA receptors in hippocampi (using immunohistochemistry and Western blot).Results Compared with control group,the step-in latency and test results of error times were significantly decreased,the expression of PSD95 and AMPA receptors in hippocampus was down-regulated,and the incidence of amnesia was increased at T1 and T2 in sevoflurane group (P＜0.05).Compared with the basic results,no significant change was found in the step-in latency or test results of error times in control group (P＞0.05),and the step-in latency and test results of error times were significantly decreased at T1 and T2 in sevoflurane group (P＜0.05).Apoptosis in pyramidal cells was not found in sevoflurane group.Conclusion Sevoflurane can inhibit the ability of memory retrieval transiently in mice,and the mechanism is related to inhibiting the expression of hippocampal PSD95 and AMPA receptors.
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Objective To evaluate efficacy of rotigaptide ZP123 on prevention of negative chronotropic effect caused by dexmedetomidine lengthening repolarization duration of the isolated rat hearts.Methods Eighteen healthy adult SD rats of either gender,weighing (300±30) g,were prepared isolated heart perfusion model by Langendorff.After 15 min perfusion and balance of K-H fluid,the isolated hearts were randomly divided into 3 groups (n=6 each): The hearts were continuously pefused for 30 min with 37℃ K-H solution in control group (group C),with dexmedetomidine 50 ng/ml in dexmedetomidine group (group D),or with rotigaptide 80 nmol/L combined with dexmedetomidine 50 ng/ml in rotigaptide combined with dexmedetomidine group (group ZD).In the whole Langendorff-perfused hearts,at the end of balanced infusion for 15 min (T0) and at 15(T1),30(T2) min of continued perfusion with K-H solution,the monophasic action potential (MAP) and heart rate (HR) were recorded from left anterior free wall,MAP duration at 50% repolarization (MAPD50) and at 90% repolarization (MAPD90),monophasic action potential amplitude (MAPA) and maximal velocity (Vmax) were calculated.Results Compared with T0,HR in group D was significantly declined at T1,T2;MAPD90 and MAPD50 in group D were significantly increased at T1,T2 (P<0.05).Compared with groups C and ZD,HR in group D was significantly declined at T1,T2;MAPD90 and MAPD50 in group D were significantly increased at T1,T2 (P<0.05).There was no significant difference in MAPA and Vmax between the three groups.Conclusion Rotigaptide antagonizes negative chronotropic effect induced by dexmedetomidine through shortening monophasic action potential duration in the myocardium of left ventricle of the isolated rat hearts.
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Objective To evaluate the effects of dexmedetomidine on the electrophysiological stability of ventricular myocardium and the expression of gap junction connexin43 (Cx43) in rats in an in vitro experiment.Methods Healthy adult Sprague-Dawley rats of both sexes,weighing 270-330 g,were anesthetized with 3.0％ pentobarbital sodium 50 mg/kg.Their hearts were excised and retrogradely perfused in a Langendorff apparatus with K-H solution saturated with 95％ 02-5％ CO2 at 37 ℃.Twelve isolated rat hearts were divided into 2 groups (n =6 each) using a random number table:control group (group C) and dexmedetomidine group (group D).After 15 min of perfusion with K-H solution,hearts were continuously perfused for 30 min with K-H solution in group C or with K-H solution containing dexmedetomidine 50 ng/ml in group D.The monophasic action potential (MAP) and ventricular effective refractory period (VERP) of the left ventricular myocardium were recorded.Myocardial MAP duration at 90％ repolarization (MAPD90) and the ratio of VERP to MAPD9.(VERP/MAPD90) were calculated.Repetitive regular stimuli (S1) were followed by a single extrastimulus (S2),and the longest pacing cycle length of ventricular fibrillation threshold and development of ventricular arrhythmia were recorded.Left ventricular myocardial tissues were obtained for detection of the expression of myocardial Cx43 by Western blot.Results Compared with group C,the MAPD90 and VERP were significantly prolonged,VERP/MAPD90 ratio was decreased,the longest pacing cycle length of ventricular fibrillation threshold was prolonged,the incidence of ventricular arrhythmia was increased,and the expression of myocardial Cx43 was down-regulated in group D (P＜ 0.05).Conclusion Dexmedetomidine can decrease the electruphysiological stability of ventricular myocardium and down-regulate the expression uf Cx43,thus increasing the risk of arrhythmia in rats in an in vitro experiment.
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Objective To investigate influence of dexmedetomidine on postoperative cognitive function in elder patients after hip re-placement surgery under spinal anesthesia. Methods Forty elderly patients with ASAⅠ~Ⅲ,undergoing hip replacement with spinal anesth-sia,were randomly divided into dexmedetomidine group( group A) and normal saline group( group B) ,with 20 patients in each group. Dexme-detomidine was given with 1 μg/kg after anesthesia and followed with 0. 5 μg·kg-1 ·h-1 in group A. The equal volume of normal saline was infused in group B. Cognitive function was evaluated before anesthesia,3 and 7 days after surgery by mini-mental state examination( MMSE) . The intraoperative concentration of TNF-α,IL-6,MDA were detected at the time of before surgery(T0),end of surgery(T1),3 days after sur-gery(T2),7 days after suegery. Results There was no significant difference in MMSE score before anesthesia between the two groups (P>0. 05). The difference of MMSE score at postoperative 3 days between two groups was statistical significance (P0. 05). Compared with T0,the concentration of TNF-α,IL-6,MDA at T1,T2 in group B increased,the difference was significant. And the concentration of IL-6 at T1 in group A decreased,compared with that at T0,the difference was significant(P<0. 05). The concentra-tion of TNF-α,IL-6 at T1,T2 and MDA at T2 in group A were lower than those in group B,the difference was significant. (P<0. 05). Con-clusion Dexmedetomidine can decreased the concentration of TNF-α,IL-6,MDA,and improve the postoperative cognitive dysfunction of eld-erly patients who finished the hip replacement surgery under spinal anesthesia.