Objective To compare the protective effect of different dose of penehyclidine hydrochloride (PHC) in rats with myocardial ischemia/reperfusion (I/R) injury.Methods Forty-eight healthy male Wistar rats were randomly divided into six groups (n =8 each):sham group,sham + 1.0 mg/kg PHC group (sham + H-PHC group),I/R group,I/R + 0.1 mg/kg PHC preconditioning group (I/R + L-PHC group),I/R + 0.3 mg/kg PHC preconditioning group (I/R + M-PHC group),and I/R + 1.0 mg/kg PHC preconditioning group (I/R + H-PHC group).I/R injury model was reproduced by ligation followed by release of the coronary artery,and PHC in different dosages was given at 30 minutes before model reproduction.At 3 hours after reperfusion,the left ventricular end-diastolic pressure (LVEDP),left ventricular end-systolic pressure (LVESP),ejection fraction (EF),and fractional shortening (FS) were recorded.The levels of aspertate aminotransferase (AST),MB isoenzyme of creatine kinase (CK-MB),and lactate dehydrogenase (LDH) were determined.The myocardial tissues were harvested for the determination of the area at risk (AAR) and the infarct area (AI),and the percentage of AI/AAR was calculated.The examination of myocardial fiber was performed with electron microscopy.Results Compared with sham and sham + H-PHC groups,LVEDP was increased in I/R groups,LVESP,EF and FS were decreased,and the levels of AST,CK-MB and LDH,as well as the AI/AAR were increased.Compared with I/R group,in pretreatment groups with different doses of PHC,LVEDP was decreased,LVESP,EF and FS were increased,the levels of AST,CK-MB,LDH,and AI/AAR were also decreased,especially in I/R+M-PHC and I/R+H-PHC groups [LVEDP (mmHg,I mmHg =0.133 kPa):11.33± 1.17,9.85± 1.09 vs.15.82 ± 1.79,LVESP (mmHg):98.9 ± 10.6,112.8 ± 10.0 vs.87.8 ± 9.2,EF:0.681 ± 0.074,0.741 ± 0.070 vs.0.569 ± 0.072,FS:(42.4 ± 4.6)％,(46.0 ± 5.1)％ vs.(36.8 ± 3.9)％,AST (U/L):386.97 ± 80.65,298.31 ± 54.88 vs.603.47 ± 173.66,CK-MB (U/L):3.12 ± 0.84,2.88 ± 0.72 vs.7.14 ± 1.54,LDH (U/L):1 784.23 ± 488.49,1 629.37 ± 436.34 vs.2 489.14 ± 460.80,AI/AAR:0.284 ± 0.014,0.223 ± 0.008 vs.0.377 ± 0.011,all P ＜ 0.05].There was significant difference in LVEDP,LVESP,and AI/AAR between I/R + M-PHC group and I/R + H-PHC group (all P ＜ 0.05),and no significant difference in other parameters (all P ＞ 0.05).It was showed by electron microscopic examination that after I/R injury,the myocyte mitochondria membranes were broken,mitochondria were markedly swollen,mitochondrial cristae disappeared;however in I/R+M-PHC and I/R+H-PHC groups,mitochondrial swelling was mild,the capsule was more or less intact,mitochondrial cristae were partly visible,the structure was complete,especially in the group I/R+H-PHC,and the mitochondrial structure was close to normal.Conclusions PHC could protect myocardial from I/R injury.Mid dose of PHC (0.3 mg/kg) and high dose of PHC (1.0 mg/kg) could provide better protective effect than low dose of PHC (0.1 mg/kg),and high dose of PHC is better in effect than the middle dose.

Objective To study the impact of severe idiopathic pulmonary arterial hypertension (IPAH) on pregnancy outcome and to investigate the effect of multidisciplinary approach during pregnancy on the pregnancy outcome in pregnant woman with severe IPAH.Methods Between March 2007 and November 2013,10 pregnant women with severe IPAH undergoing treatment in Beijing Anzhen Hospital were studied retrospectively.Hemodynamic measurements,medical therapy,manner of delivery,anesthetic administration,multidisciplinary management and outcomes were assessed.Results All 10 cases were first diagnosed at the mean of (24 ± 3) weeks during the pregnancy.The systolic pulmonary artery pressure (sPAP) estimated by transthoracic echocardiography was (95.6 ± 1.3) mmHg (1 mmHg =0.133 kPa).Seven cases of class Ⅲ and 3 cases of class Ⅳ were recorded by World Health Organization functional class.One patient underwent pregnancy termination at gestational age of 21 weeks with no maternal death or complications,nine patients continued pregnancy and all the patients underwent cesarean section.The mean pregnancy length was (31 ± 5) weeks.Nine had cesarean deliveries during continuous epidural anesthesia,and one during general anesthesia.There were three maternal deaths in hospital (5,2,3 days postpartum),and seven patients were alive,and the average hospitalization days was (8 ± 4) days.One fetus lost with cesarean section.Two were term delivery,and seven cases were premature delivery.The average weight is (1 948 ± 731) g and nine were alive and no malformation.Conclusions Because of maternal mortality in patients with severe IPAH remains prohibitively high,patients should continue to be counseled to avoid pregnancy.Women with severe IPAH who become pregnancy should be followed by multidisciplinary approach,and cesarean deliveries during continuous epidural anesthesia are a relatively safe way for pregnancy termination in patients with severe IPAH.

Objective To evaluate the efficacy of nalmefene antagonizing postoperative respiratory depression induced by opioids.Methods Two hundred and forty ASA Ⅰ orⅡpatients aged 18-64 yr with body weight fluctuating within 20% of the standard body weight were included in this multicenter,randomized,double-blind,positive drug-controlled study.Anesthesia was induced with etomidate 0.3 mg/kg and TCI of sufentanil(effect-site concentration 0.4.ng/ml).Tracheal intubation was facilitated with vecuronium 0.1 mg/kg or rocuronium 0.6mg/kg.The patients were mechanically ventilated.PETCO2 was maintained at 35-45 mm Hg.Anesthesia was maintained with sevoflurane+ sufentanil TCI(Ce=0.1-0.4 ng/ml).Patients undergoing neurosurgery and liver or kidney operation were excluded.The operation time was within 3 h.The residual effects of muscle relaxants were reversed after operation.The patients were randomly divided into 2 groups(n=120 each):group Ⅰneloxone andgroup Ⅱ nalmefene.Naloxone 0.1 mg or nalmefene 0.25 μg/kg was injected iv over 30 s and was repeated 5 min later if necessary until the respiratory rate＞10 bpm,PETCO2＜45 mm Hg and apnea time＜15 s.The total amount of naloxone was≤0.4 mg while that of nalmefene≤1 μg/kg.BP,HR,SpO2,PETCO2,respiratory rate and apnea time were recorded immediately before and at 2 and 5 min after haloxone/nalmefene administration and then every 5 min until 5 min after extubation.The recovery of spontaneous breathing within 30 min after naloxone/nalmefene administration,extubation time and Ramsay sedation score at 5 min after extubation were recorded.The patients were also observed for adverse reactions.Results Spontaneous breathing recovered within 30 min after naloxone/nalmefene administration in all patients in both groups.The extubation time was significantly shorter in nalmefene group than in naloxone group.There was no significant difference in Ramsay sedation score,BP,HR,SpO2 and incidence of adverse reactions between the 2 groups.Conclusion Nalmefene is better than naloxone in antagonizing opioid-induced postoperative respiratory depression.

Objective To evaluate the effect of preconditioning with penehyclidine hydrochloride (PHC)on mitochondria-dependent pathway of apoptosis during myocardial ischemia-reperfusion(I∕R)in rats. Methods Twenty-four healthy adult male Wistar rats were allocated into 3 groups(n=8 each)using a random number table: sham operation group(group S), I∕R group and PHC preconditioning group (group P). Myocardial I∕R was produced by occlusion of left anterior descending branch of coronary artery for 30 min followed by 3 h reperfusion. PHC 10 mg∕kg was injected via the tail vein at 30 min before oc-clusion in group P. The rats were sacrificed at the end of reperfusion, hearts were removed and left ventric-ular specimens were obtained for determination of apoptosis in cardiomyocytes(by TUNEL), and apoptosis index(AI)was calculated. Mitochondria and cytoplasm were isolated for detection of mitochondrial mem-brane potential(MMP, by JC-1 method)and expression of Bcl-2, cytochrome c(Cyt c)in mitochondri-a and cytoplasm and activated caspase-3 in myocardial tissues(by Western blot). Results Compared with group S, AI was significantly increased, the expression of Bcl-2 and mitochondrial Cyt c was down-regula-ted, MMP was decreased, and the expression of Cyt c in cytoplasm and activated caspase-3 was up-regula-ted in I∕R and P groups(P<0. 05). Compared with group I∕R, AI was significantly decreased, the ex-pression of Bcl-2 and mitochondrial Cyt c was up-regulated, MMP was increased, and the expression of Cyt c in cytoplasm and activated caspase-3 was down-regulated in group P(P<0. 05). Conclusion The mechanism by which PHC preconditioning attenuates myocardial I∕R injury is related to inhibiting mitochon-dria-dependent pathway of apoptosis in rats.

Objective To investigate the protective effect of dynamin-related protein 1 (Drp1) in rats with myocardial ischemia/reperfusion injury (IRI).Methods Twenty-four healthy male Wistar rats were randomly divided into three groups (n = 8 each): sham group, IRI model group, and Drp1 inhibitor group. The left anterior descending branch of coronary artery was ligated to produce myocardial ischemia for 30 minutes and reperfusion injury model. Sham group was received only threading without ligation. The Drp1 inhibitor group was injected with 1.2 mg/kg mitochondrial division inhibitor 1 (mdivi-1) at 15 minutes before operation. At 3 hours after reperfusion, hemodynamics, serum myocardial enzymes, mitochondrial membrane potential (MMP), hydrogen peroxide (H2O2), reactive oxygen species (ROS) and ATP production were measured in rats. The myocardial tissues were harvested for the determination of the area at risk (AAR) and the infarct area (AI), and the ratio of AI/AAR was calculated. The expression of Drp1 and cytochrome C (Cyt C) was determined by Western Blot.Results Compared with the sham group, the left ventricular end diastolic pressure (LVEDP), cardiac troponin I (cTnI), MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), AI/AAR, H2O2, ROS, protein expression of Drp1 and Cyt C were significantly increased, left ventricular end systolic pressure (LVESP), ejection fraction (EF), fractional shortening (FS), MMP, ATP generation, expression of mitochondrial Cyt C were significantly decreased in IRI model group. Compared with IRI model group, LVEDP was significantly decreased in Drp1 inhibitor group [mmHg (1 mmHg = 0.133 kPa): 8.83±1.20 vs. 16.48±1.80], LVESP, EF, FS were significantly increased [LVESP (mmHg): 116.80±9.78 vs. 87.80±8.82, EF: 0.78±0.11 vs. 0.58±0.07, FS: (48.6±4.1)％ vs. (32.4±3.2)％];myocardial enzymes, H2O2 and ROS were significantly decreased in Drp1 inhibitor group [cTnI (ng/L): 31.9±8.8 vs. 49.2±13.7, CK-MB (U/L): 4.83±1.30 vs. 7.48±2.20, LDH (U/L): 1327.80±280.20 vs. 1858.80±324.80, H2O2:6.40±1.40 vs. 8.90±1.50, ROS: 41916.3±6295.3 vs. 65182.6±3777.8], AI/AAR was significantly decreased (0.38±0.01 vs. 0.62±0.01), MMP and ATP were significantly increased [MMP: 0.78±0.13 vs. 0.38±0.07, ATP (μmol/g): 150.8±12.3 vs. 103.7±8.4], the expression of Drp1 was significantly decreased (0.50±0.02 vs. 0.79±0.05), expression of mitochondria Cyt C was significantly increased (0.64±0.04 vs. 0.21±0.01), and expression of cytoplasmic Cyt C was significantly decreased (0.48±0.03 vs. 0.78±0.04), and the differences were statistically significant (allP <0.05).Conclusions Mitochondrial fission was excessively high during IRI, and its function was significantly decreased. Drp1 inhibitor could inhibit the division of mitochondria, and improve its function and cardiac function.

Objective:To examine the effects of low-dose Esketamine on circulatory function, respiratory function and pain in elderly patients undergoing peripheral vascular interventions, and to provide evidence for appropriate and safe use of Esketamine in elderly patients under anesthesia.Methods:Forty elderly patients with iliac artery stenosis at Beijing Anzhen Hospital affiliated to the Capital Medical University were enrolled and treated with balloon percutaneous transluminal angioplasty(PTA)and stent implantation on a selective basis.Among them, 33 were male and 7 were female with American Society of Anesthesiologists(ASA)physical classification of Ⅱ-Ⅲ.The patients were randomly divided into two groups(20 in each group)using the randomized number method, with the control group(Group C)given 2 ml normal saline intravenously and the Esketamine group(Group L)given Esketamine 0.25 mg/kg intravenously(slow intravenous administration within 1 min). Values of arterial blood pressure and heart rate in stabilized condition in the operating room were collected as the baseline(T0). Five minutes before the surgeon dilated the stenosed iliac artery, intravenous anesthetics were given in both groups as required for the trial.The first 5 minutes before dilatation of the stenosed iliac artery was used as T1, the first 4 minutes as T2, and the first 3 minutes as T3.The recording continued until the 25th minute after anesthetic administration as T30, with a collection of 25-minute blood pressure and heart rate values for analysis.Blood gas analysis was made for arterial blood samples drawn at the time patients entered the operating room(M1), 5 minutes after drug administration(M2), and 10 minutes after drug administration(M3). For all patients, the pain level was recorded using a self-reported scale while the iliac artery was dilated.The doses of vasoactive drugs were recorded from the beginning of the dilatation of the iliac artery to the end of the procedure in patients.Results:In Group C, PaO 2 at M2 was elevated compared with at M1( P=0.003); In Group L, PaCO 2 at M2 was elevated compared with at M1( P=0.011). At T4, systolic blood pressure and diastolic blood pressure were elevated in Group L compared with Group C, and the differences were statistically significant( t=2.403, 2.119, all P<0.05); At T3, heart rate was elevated in Group L compared with Group C, with a statistically significant difference( t=0.789, P=0.007); Compared with Group C, systolic blood pressure was lower in Group L from T6 to T15, with statistically significant differences( t=3.143, 2.403, 2.272, 3.460, 2.610, 2.568, 2.453, 2.367, 2.282, and 2.187, all P<0.05). Diastolic blood pressure was lower in Group L from T8 to T16, with statistically significant differences( t=3.880, 6.602, 2.967, 3.243, 2.641, 3.253, 3.114, 4.521, and 2.659, all P<0.05), and from T7 to T13, the heart rate was lower in Group L, and the differences were statistically significant( t=2.246, 3.285, 3.207, 2.752, 2.725, 2.713, and 2.473, all P<0.05). Compared with Group C, the incidence of dilatation pain in patients with iliac artery stenosis in Group L was lower, and the difference was statistically significant( χ2=6.140, P=0.030). Doses of vasoactive drugs in both groups, including raceanisodamine hydrochloride, norepinephrine, esmolol, and nicardipine, were lower in Group L, and the differences were statistically significant( t=3.573, 7.883, 3.889, and 6.665, P=0.039, 0.001, 0.046, and 0.006). Conclusions:Low-dose Esketamine causes mild respiratory depression and low circulatory excitation in elderly patients with iliac artery stenosis undergoing PTA, and also reduces painful irritation during blood vessel dilatation in elderly patients.

Objective To observe the relationship between Flo Trac/Vigileo monitor-assessed stroke volume variability(SVV) and changes in ventilation volume during one lung ventilation(OLV),and to evaluate the feasibility of SVV reflecting changes in lung ventilation volume during OLV in patients with elderly coronary heart disease.Methods A total of 40 patients with ASA grade Ⅱ or Ⅲ,aged 60-82 years,undergoing elective thoracoscopic surgery were enrolled in this study.A doublelumen endobronchial tube was inserted,and 6％ hydroxyethyl starch(HES 130/0.4)was infused intravenously for five dosage-infusion-stage of(T0)2 ml/kg,(T1)4 ml/kg,(T2)6 ml/kg,(T3)8 ml/kg,(T4)10 ml/kg.And the infusion was suspended until starting next infusion stage.After the data reached the stability,the mean arterial pressure(MAP),heart rate(HR),central venous pressure (CVP),cardiac output(CO)and SVV were recorded.The test was stopped after stage of(T4)10 ml/kg.Then,we observed and analyzed the changes of MAP,HR,CVP,CO and SVV at different time points.Results The statistically significant difference was not found in MAP(F =2.089,P =0.130),but was definitely found in SVV,HR,CO and CVP between five different time points(F =23.380,15.205,14.990,4.726,P=0.000,0.060,0.000 and 0.001,respectively).SVV(％) was 12.6 ± 1.8 at T0,10.7 ± 1.7 at T1,9.7 ± 1.3 at T2,8.6 ± 1.2 at T3,7.8 ± 1.2 at T4,with a gradually decreased trend(P =0.000,0.000,0.042,0.033,between any two adjacent time points,respectively).While CVP had no significant difference between any two adjacent time points (P =0.093,0.161,0.261 and 0.051,respectively).HR was lower in T1 vs.in T0,and in T2 vs.in T1 (P =0.015 and 0.028,respectively).There was no significant difference in HR between the other time points (P =0.149 and 0.335,respectively).The CO was higher at T4 than at T3(P =0.005),and there was no significant difference among any other time points(T0 vs.T1,T1 vs.T2,T2 vs.T3,P =0.547,0.441 and 0.400,respectively).In Spearman correlation analysis,the amount of HES infusion was positively correlated with MAP(r =0.921,P =0.021),negatively correlated with SVV and HR(r =-0.988,-0.984,P=0.001,0.002,respectively),and not correlated with CVP and CO(r =0.872 and 0.871,P =0.054 and 0.055,respectively).Conclusions SVV can effectively evaluate the volume responsiveness in elderly CHD patients with OLV.

Objective To investigate the risk factors for postoperative prolonged mechanical ventilation in neonates and young infants with complicated congenital heart disease. Methods A retrospective analysis of 150 children (80 males and 70 females, aged ≤ 6 months, RACHS-1 grade ≥ 3) with complex congenital heart disease who were admitted to Children's Heart Surgery Department of Anzhen Hospital from January 2016 to December 2017 was conducted. These data were collected: the demographic data, history of cardicvascular-related diseases, type of surgery, preoperative complications, CPB, CPB time, deep hypothermia, blood gas index, delayed chest closure (DCC), pacemaker; minimum oxygenation index in the first 24 h after operation, maximum vasoactive-inotropic score (VIS), failed extubation and postoperative complications. Logistic regression model was used to analyze the risk factors of prolonged mechanical ventilation within neonates and young infants after complicated congenital heart surgery. Results Forty-two patients (28％) required PMV with mechanical ventilation ≥ 72 h. Univariate analysis showed age, weight, RACHS-1 grade, previous history of cyanosis, history of pneumonia, emergency surgery, preoperative mechanical ventilation, preoperative EF, deep hypothermia, CPB time＞ 132 min, intraoperative minmum pH value, intraoperative maximum blood glucose and lactic acid concentrations, DCC, application of pacemakers, maximum VIS within 24 h after surgery, minimal OI and postoperative complications may be the risk factors of prolonged postoperative mechanical ventilation in neonates and young infants with complicated congenital heart disease (P ＜ 0.05). Multivariate Logistic regression analysis showed that the CPB time＞132 min (OR = 11.04, 95％ CI 2.07-58.96, P = 0.005), intraoperative maximum lactate (OR = 1.53, 95％ CI 1.07-2.20, P = 0.021) and failed extubation (OR = 17.28, 95％ CI 2.46-121.20, P = 0.004) were independent risk factors for prolonged postoperative mechanical ventilation in neonates and young infauts with complicated congenital heart disease. Conclusion CPB time＞132 min, intraoperative maximum lactic acid concentration and failure of extubation can be used as predictors of prolonged postoperative mechanical ventilation in neonates and young infants with complicated congenital heart disease.