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Objective:To investigate the effects of dexmedetomidine on the myocardial electrical conduction velocity and the expression and distribution of connexin 43 (Cx43) in rats.Methods:Healthy adult Sprague-Dawley rats of both sexes, weighing 270-330 g, were used.Twelve isolated rat hearts successfully perfused in the Langendorff apparatus were divided into 2 groups ( n=6 each) using a random number table method: control group (group C) and dexmedetomidine group (group D). The hearts were perfused for 15 min with K-H solution, and then the hearts were continuously perfused for 30 min with 37 ℃ K-H solution in group C and with K-H solution containing dexmedetomidine 50 ng/ml in group D. Programmed electrical stimulation was performed after the end of perfusion, the activation latency was recorded, and the electrical conduction velocity of myocardial tissues was calculated, and then the left ventricular myocardial tissues were obtained for determination of the expression and distribution of myocardial Cx43 protein by immunohistochemistry method. Results:Compared with group C, the activation latency was significantly prolonged, the electrical conduction velocity was reduced, and the expression of Cx43 was down-regulated in group D ( P<0.05). Cx43 protein was mostly distributed in intercalated discs at both ends of cells in group C, and there was a tendency for the proteins localized at end-to-end contact sites of ventricular cardiomyocytes to localize at side-to-side contact sites, and the distribution was messy in group D. Conclusions:Dexmedetomidine causes arrhythmia probably through down-regulating the expression of Cx43 protein, changing its distribution, and reducing myocardial electrical conduction velocity in rats.
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Objective To evaluate the role of sarcolemmal ATP-sensitive potassium ( sarcKATP ) channel in sevoflurane-induced maintenance of electrophysiological stability of ventricular myocardium in di-abetic rats. Methods Clean-grade healthy male Sprague-Dawley rats, aged 3 months, weighing 280-320 g, in which diabetes mellitus ( DM) was induced by intraperitoneal streptozotocin 60 mg/kg and confirmed by blood glucose ≥16. 7 mmol/L, were used in this study. Their hearts were excised after anesthesia and retrogradely perfused in a Langendorff apparatus at 4 weeks after establishing the DM model. Twenty-four Langendorff-perfused hearts were divided into 3 groups ( n=8 each) using a random number table method:DM group ( group D) , DM plus sevoflurane group ( group DS) and DM plus sevoflurane plus HMR-1098 group (group DSH). Another 8 Langendorff-perfused hearts of normal rats were selected as control group ( group C) . Hearts were perfused with 37℃ K-H solution via the aorta in each group, 15 min of equilibra-tion later hearts were continuously perfused for 30 min with K-H solution in C and D groups, with K-H solu-tion saturated with 2. 5％ sevoflurane in group DS, or with K-H solution saturated with 10 μmol/L HMR-1098 and 2. 5％ sevoflurane in group DSH. Monophasic action potential (MAP) duration at 50％ and 90％repolarization ( MAPD50 and MAPD90 ) in the endocardium and epicardium of the left ventricular anterior wall were recorded at 15 min of equilibration ( T0 ) and 15 and 30 min of reperfusion ( T1,2 ) , transmural dispersion of repolarization ( TDR) was calculated. S1S2 program-controlled stimulation was performed at the end of perfusion to record the effective refractory period (ERP), ventricular arrhythmia (VA) induced and the longest pacing cycle length ( PCL) of ventricular fibrillation threshold ( VFT) induced. ERP/MAPD90 ratio was calculated. Results Compared with group C, TDR was significantly increased at T0 , ERP/MADP90 ratio was decreased, the incidence of VA induced was increased, and the longest PCL of VFT induced was prolonged in group D ( P＜0. 05) . Compared with group D, TDR was significantly decreased at T2 in group DS (P＜0. 05), and ERP/MADP90 ratio was significantly increased, the incidence of VA in-duced was decreased, and the longest PCL of VFT induced was shortened in DS and DSH groups ( P＜0. 05). TDR was significantly smaller at T2 in group DSH than in group DS (P＜0. 05). Conclusion sarcKATP channel is involved in sevoflurane-induced maintenance of electrophysiological stability of ventricu-lar myocardium in diabetic rats.
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Objective To investigate the electrophysiological protective effect of HTK solution containing sevoflurane on rat cardiac transplantation. Methods Twenty-four male Sprague-Dawley rats were divided into the control group,sevoflurane group and Heptanol group. Rat hearts in 3 groups were stored in HTK solution,containing sevoflurane and sevoflurane+heptanol HTK solution for 6 h. Heart resuscitation time,the duration of arrhythmia and monophasic action potential(MAP)and heart rate(HR)at different time points were recorded.Monophasic action potential duration of repolarization at 50% and 90%(MAPD50 and MAPD90),monophasic action potential amplitude(MAPA)and maximal velocity(Vmax)were analyzed. Results The isolated rat hearts in each group can be successfully restored to the spontaneous heart beat. Compared with group C ,heart resuscitation time in group S and group H was significantly shortened,heart rate(HR)was significantly decreased at T1,MAPD50 and MAPD90 in heart intima and epicardium were shortened at T1 ~ T2,the incidence of ventricular fibrillation and reperfusion arrhythmia Scores were reduced,with the shorter duration of ventricular fibrillation(P<0.05). No significant difference was found in Vmax and MAPA among the three groups at each time point. Conclusion HTK solution containing sevoflurane and HTK solution containing heptanol had similar electrophysiological effects ,which could inhibit the prolonged monophasic action potential(MAP)and reduce arrhythmia. The electrophysiological protective effect of HTK solution containing sevoflurane may be associated with the inhibition of gap junction function.
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Objective To systematically evaluate the effect of intranasal dexmedetomidine on agita-tion during emergence from general anesthesia with sevoflurane in pediatric patients. Methods Pubmed, Embase, The Cochrane Library, China National Knowledge Infrastructure, VIP, Wan-Fang databases were searched for randomized controlled trials involving the effect of intranasal dexmedetomidine on agitation during emergence from general anesthesia with sevoflurane in pediatric patients from the start of their data-base until June 2017, and the reference lists of all included studies were checked manually. Data were ex-tracted independently by two reviewers, and primary evaluation indexes included the incidence of emergence agitation and sedation score. Secondary evaluation indexes included emergence time, extubation time, du-ration of post-anesthesia care unit stay, postoperative consumption of analgesics, incidence of adverse reac-tions ( such as bradycardia, nausea and vomiting, pruritus, laryngeal spasm) during recovery from anes-thesia. The quality of methodology of included studies was assessed. Meta-analysis was conducted with Rev-Man 5. 3 software. Results Eight randomized controlled trials involving 520 pediatric patients were includ-ed in this meta-analysis. Compared with placebo group, the incidence of emergence agitation was signifi-cantly decreased, sedation score was increased, extubation time was prolonged ( P<0. 05) , no significant change was found in the duration of post-anesthesia care unit stay or incidence of postoperative nausea and vomiting in intranasal dexmedetomidine group ( P>0. 05) . The emergence time was prolonged in intranasal 0. 3-1. 0 μg∕kg dexmedetomidine group ( P<0. 05 ) , and no significant change was found in emergence time in intranasal dexmedetomidine 1. 0-2. 0μg∕kg group ( P>0. 05) . Conclusion Intranasal dexmedeto-midine can decrease the occurrence of agitation during emergence from general anesthesia with sevoflurane and raise the quality of emergence in pediatric patients.
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Objective To evaluate the effect of sevoflurane-containing HTK solution on electro-physiological stability of rat donor heart during reperfusion. Methods Male Sprague-Dawley rats, weighing 280-320 g, aged 3 months, in which a Langendorff-perfused isolated rat donor heart model was estab-lished, were used in this study. Sixteen donor hearts were obtained and divided into 2 groups (n＝8 each) using a random number table method: control group (group C) and sevoflurane group (group S). HTK so-lution was used as preservation solution in group C. HTK solution containing 2. 5% sevoflurane was used as preservation solution in group S. Hearts were stored for 6 h in the corresponding preservation solution at 4℃ and then reperfused, and the perfusion temperature was gradually restored to 37 ℃ in two groups. The time of spontaneous recovery of heart beat and development of arrhythmia were recorded. Heart rate, monophasic action potential (MAP) duration at 50% and 90% repolarization (MAPD50, MAPD90), MAP amplitude and maximum velocity and development of early after-depolarization and delayed after-depolariza-tion were recorded at 30 and 45 min of reperfusion. Results Compared with group C, the time of sponta-neous recovery of heart beat was significantly shortened, the incidence of ventricular fibrillation and arrhyth- mia score were decreased, the ventricular fibrillation interval was shortened, and MAPD50and MAPD90of epicardium and endocardium were shortened at 30 and 45 min of reperfusion (P＜0. 05), and no significant change was found in hear rate, maximum velocity or MAP amplitude in group S (P＞0. 05). Early after-de-polarization and delayed after-depolarization were not found in two groups. Conclusion Sevoflurane-contai-ning HTK solution can maintain electrophysiological stability of rat donor heart during reperfusion and de-crease the occurrence of arrhythmia.
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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 the role of δ-opioid receptors in hydromorphone postcondition-ing-induced maintenance of electrophysiological stability during ischemia-reperfusion(I∕R)in isolated rat hearts. Methods Healthy male Sprague-Dawley rats, aged 2-3 months, weighing 280-360 g, were used in this study. The animals were anesthetized with intraperitoneal pentobarbital 60 mg∕kg. Their hearts were immediately removed and perfused in a Langendorff apparatus. Thirty-two isolated hearts were divided into 4 groups after successful preparation of Langendorff perfusion model(n=8 each)using a random number ta-ble: control group(group C), group I∕R, hydromorphone postconditioning group(group HP)and hydro-morphone plus δ-opioid receptor antagonist naltridole postconditioning group(group HNP). In HP and HNP groups, the hearts were perfused for 10 min with K-H solution containing 41 ng∕ml hydromorphone and 41 ng∕ml hydromorphone plus 5 μmol∕L naltridole, respectively, and then with K-H solution for 50 min. At 20 min of stabilization(T0)and 10, 25 and 60 min of reperfusion(T1-2), heart rate(HR), monophasic action potential(MAP)duration at 90% repolarization(MAPD90)of the two layers(endocar-dium, epicardium)of the anterior left ventricular wall were recorded. Transmural dispersion of repolariza-tion(TDR)was calculated. The development of arrhythmia, time for restoration of spontaneous heart beat and duration of arrhythmia were recorded during the period of reperfusion. Results Compared with group C, MAPD90of endocardium at T1-2and MAPD90of epicardium at T1were significantly prolonged in I∕R and HP groups, HR was significantly decreased at T2-3, MAPD90of endocardium and epicardium was prolonged at T1-3in group HNP, TDR was significantly enlarged at T1in group I∕R and at T2in group HNP, and TDR was decreased at T3in group HP(P<005). Compared with group I∕R, no significant change was found in arrhythmia score(P>005), the time for restoration of spontaneous heart beat was significantly shortened, and TDR was decreased at T1in HP and HNP groups, duration of arrhythmia was significantly shortened, and MAPD90of endocardium was shortened at T1in group HP, and HR was significantly decreased at T2-3, MAPD90of endocardium and epicardium was prolonged at T1-3, and TDR was decreased at T2-3in group HNP(P<005). Compared with group HP, no significant change was found in time for restoration of spon-taneous heart beat, duration of arrhythmia or arrhythmia score(P>005), HR was significantly decreased at T2-3, MAPD90of endocardium and epicardium was prolonged at T1-3, and TDR was increased at T3in group HNP(P<005). Conclusion The mechanism underlying hydromorphone postconditioning-induced maintenance of electrophysiological stability during I∕R is related to activating δ-opioid receptors in isolated rat hearts.
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Objective To evaluate the effect of hydromorphone postconditioning on the electrophysiological stability during ischemia-reperfusion (I/R) in isolated rat hearts.Methods Healthy adult male Sprague-Dawley rats,aged 2-3 months,weighing 280-360 g,were heparinized and anesthetized with pentobarbital sodium.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 37 ℃.Twenty-four Langendorff-perfused hearts were divided into 3 groups (n =8 each) using a random number table:control group (group C),I/R group and hydromorphone postconditioning group (group HM).The isolated hearts were subjected to 60 min ischemia followed by 60 min reperfusion to establish the model of isolated heart I/R injury.The isolated hearts were perfused with K-H solution containing 4.1 ng/ml hydromorphone for 10 min starting from onset of reperfusion in group HM.Heart rate,electrocardiogram,coronary flow,and monophasic action potential amplitude,in the left ventricular endocardium,mid-myocardium and epicardium the maximal increase rate (Vmax) at the 0 phase,and monophasic action potential duration at 50％ and 90％ repolarization (MAPD50 and MAPD90,respectively) were recorded at 20 min of stabilization (T0) and 10,25,40 and 60 min of reperfusion (T1-4).The transmural dispersion of repolarization (TDR) was calculated,and the time for restoratiou of spontaneous heart beat was recorded.Results There was no significant difference in the heart rate,coronary flow or monophasic action potential amplitude between the three groups (P＞0.05).Compared with group C,V in the epieardium was significantly decreased,MAPD50 and MAPD90 in the three transmural layers were prolonged,and TDR was prolonged in group I/R (P＜0.05).Compared with group I/R,the time for restoration of spontaneous heart beat,MAPD50 in the endoeardium and mid-myocardium,and MAPD90 and TDR in the endocardium were significantly shortened (P＜0.05),and no significant change was found in V in group HM (P＞0.05).Conclusion Hydromorphone postconditioning is helpful in maintaining the electrophysiological stability during I/R in 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 evaluate the effect of sevoflurane on the electrophysiological stability of ventricular myocardium in diabetic rats.Methods Thirty-two pathogen-free healthy adult male Sprague-Dawley rats,aged 3 months,weighing 180-220 g,were divided into 4 groups (n=8 each) using a random number table:control group (group C),sevoflurane group (group S),diabetes mellitus group (group D) and diabetes mellitus plus sevoflurane group (group D+S).After the model of diabetes mellitus was established,the hearts were rapidly excised and perfused in a Langendorff apparatus with oxygenated (95％ O2-5％ CO2) K-H solution.After 15 min stabilization,the hearts were continuously perfused for 30 min with K-H solution in C and D groups and with K-H solution saturated with 2.5％ sevoflurane in S and D+S groups.At 15 min of stabilization (T0) and 15 and 30 min of perfusion (T1-2),heart rate (HR) and monophasic action potential (MAP) duration at 50％ and 90％ repolarization (MAPD50,MAPD90) in the two layers (endocardium,epicardium) of the anterior left ventricular wall were recorded.Transmural dispersion of repolarization (TDR) was calculated.S1S2 program-controlled stimulation was performed at the end of perfusion,and the occurrence of effective refractory period (ERP) and ventricular arrhythmia (VA) was recorded.ERP/MAPD90 was calculated.Results Compared with group C,HR was significantly decreased at T1-2 in group S,HR was significantly decreased and MAPD50 and MAPD90 in epicardium and endocardium were prolonged at T0-2 in D and D + S groups,TDR was significantly enlarged at T0and ERP/MAPD90 was decreased in group D,and the incidence of arrhythmia and induction rate of VA were significantly increased in D and D+S groups (P＜0.05).Compared with group D,TDR was significantly decreased at T2,the incidence of arrhythmia and induction rate of VA were decreased,and ERP/MAPD90 was enlarged in group D+S (P＜0.05).Conclusion Sevoflurane can enhance electrophysiological stability of ventricular myocardium in diabetic rats and decrease the risk of ventricular arrhythmia.
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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.