Objective To evaluate the effect of mild hypothermia on inositol-requiring enzyme 1 (IRE1) signaling pathway during myocardial injury after cardiac arrest and resuscitation in swine.Methods Twenty-one healthy male white swine,weighing 33-41 kg,were divided into 3 groups using a random number table method:sham operation group (group S,n =5),cardiac arrest-cardiopulmonary resuscitation group (group CA-CPR,n=8),and mild hypothermia group (group MH,n=8).The model of cardiac arrest and resuscitation was established based on the previously reported method.The catheters placed in the left femoral artery and right internal jugular vein were connected to the PiCCO Monitor system,and another pacing catheter was advanced from the right external jugular vein into the right ventricle.Ventricular fibrillation was induced by using a 1 mA alternating current through the pacing catheter.Once ventricular fibrillation was successfully induced,mechanical ventilation was discontinued for 8 min,and then cardiopulmonary resuscitation was initiated.Epinephrine 20 μg/kg was administered at 2.5 min of resuscitation followed by repetition every 3 min.Defibrillation was delivered at 5 min of resuscitation,and then spontaneous circulation was evaluated.If return of spontaneous circulation was not achieved,cardiopulmonary resuscitation was immediately resumed for 2 min and then defibrillation was delivered again.Mechanical ventilation was continued for 30 h after successful resuscitation.Animals in group S only underwent surgical preparation without experiencing cardiac arrest and resuscitation.At 5 min after successful resuscitation,body temperature was cooled down to 33 ℃ by using a cooling blanket,and then maintained at this level until 24 h after resuscitation,followed by 5 h of re-warming at a rate of 1 ℃/h in group MH.The temperature was maintained at 37.5-38.5 ℃ with the aid of surface cooling blanket in the other two groups.At 1,6,12,24 and 30 h after resuscitation (T1-5),the values of stroke volume (SV) and global ejection fraction (GEF) were recorded,and meanwhile 2 ml of blood samples was obtained via the femoral vein to measure the concentration of serum cardiac troponin Ⅰ (cTnI) (by enzyme-linked immunosorbent assay) and activity of serum creatine kinase-MB (CK-MB) (by immunosuppression).The swine were sacrificed at 30 h after resuscitation,and then myocardial specimens from the left ventricle were obtained for determination of the expression of caspase-3 (by immunohistochemistry),cell apoptosis (by TUNEL),and expression of IRE1 and casepase-12 (by Western blot).Apoptosis index was calculated.Results Compared with group S,SV and GEF were significantly decreased and the serum CK-MB activity was increased at T1-5,the concentration of serum cTnI was increased at T2-5,the expression of IRE1,caspase-12 and caspase-3 in myocardium was up-regulated,and apoptosis index was increased in CA-CPR and MH groups (P＜0.05).Compared with group CA-CPR,the SV and GEF were significantly increased and the concentration of serum cTnI was decreased at T2-5,the activity of serum CK-MB was decreased at T3-5,the expression of IRE1,caspase-12 and caspase-3 in myocardium was down-regulated,and apoptosis index was decreased in group MH (P＜0.05).Conclusion The mechanism by which mild hypothermia mitigates myocardial injury after cardiac arrest and resuscitation may be related to inhibiting IRE1 signaling pathway in swine.

Objective:To investigate the role and mechanism of sodium valproate (VPA) in cardiac and cerebral injuries after cardiopulmonary resuscitation (CPR) in pigs.Methods:Twenty-five healthy male domestic pigs, weighing (37±3) kg, were randomly divided into the sham group ( n=6), CPR group ( n=10), and CPR+VPA group ( n=9). Cardiac arrest was induced by alternating current delivered via a pacing catheter in the right ventricle and untreated for 9 min, and then CPR was performed for 6 min, in which this procedure was used to establish the animal model of cardiac arrest and CPR. At 5 min after resuscitation, a dose of 150 mg/kg of VPA was infused with a pump via the femoral vein in 1 h in the CPR+VAP group. At 1 h, 2 h, 4 h and 24 h after resuscitation, blood samples were drawn from the femoral vein, and then used to measure the serum concentrations of cardiac troponin I (cTnI), creatine kinase MB (CKMB), neuron specific enolase (NSE), and S100B protein (S100B) by ELISA. At 24 h after resuscitation, the animals were euthanized, and then tissue specimens in the left myocardium and brain cortex were rapidly harvested to detect the expression levels of C/EBP homologous protein (CHOP), caspase 12, and caspase 3 by Western blot, and the rate of apoptotic cells was detected by TUNEL. Continuous variables were compared with one way analysis of variance among the three groups. Results:(1) After resuscitation, cardiac and cerebral injury biomarkers including cTnI, CKMB, NSE, and S100B in serum were significantly increased in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). The serum concentrations of cTnI and NSE starting 1 h after resuscitation and the serum concentrations of CKMB and S100B starting 2 h after resuscitation were significantly decreased in the CPR+VPA group compared to the CPR group (all P<0.05). (2) Those proteins related to cell apoptosis mediated by endoplasmic reticulum stress, including CHOP, caspase 12, and caspase 3, were significantly increased, and meanwhile apoptosis index was markedly elevated after resuscitation in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). Nevertheless, the expression levels of CHOP, caspase 12, and caspase 3 were significantly decreased, and cell apoptosis was markedly reduced in the heart and brain after resuscitation in the CPR+VPA group compared to the CPR group (all P<0.05). Conclusions:VPA can alleviate cardiac and cerebral injuries after CPR in pigs, and its mechanism may be possibly related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.

Objective: To investigate the resuscitation effect of aortic balloon occlusion (ABO) on the traumatic cardiac arrest (TCA) in swine. Methods: Twenty-seven male domestic swine weighing (32.7±3.8)kg were utilized. After 40% of estimated blood volume was removed within 20 minutes, the animals were subjected to 5 minutes of untreated ventricular fibrillation and then 5 minutes of cardiopulmonary resuscitation. Additionally, fluid resuscitation was initiated coincident with the beginning of cardiopulmonary resuscitation. The animals were randomly divided into model group (n=12) and ABO group (n=15). Once cardiopulmonary resuscitation was implemented, aortic balloon was concurrently inflated to stop the blood flow of descending thoracic aorta at the level of the diaphragm in the ABO group. In the model group, aortic balloon was placed in the same position without inflation. During cardiopulmonary resuscitation, the changes of coronary perfusion pressure (CPP), forehead's regional cerebral oxygen saturation (rSO₂) and pressure of end-tidal CO₂ (PETCO₂) were continuously monitored, and the rate of return of spontaneous circulation (ROSC), duration of cardiopulmonary resuscitation, number of shocks and dose of epinephrine were recorded. At 5 minutes after successful resuscitation, the levels of arterial blood gas, lactate and jugular venous blood oxygen saturation (SjvO₂) were measured. Results: Compared with the model group, the values of CPP, rSO₂ and PETCO₂ during cardiopulmonary resuscitation were significantly increased in the ABO group [CPP: (33.5±5.6)mmHg vs. (23.1±5.2)mmHg at 1 minute, (35.3±6.0)mmHg vs. (26.8±7.4)mmHg at 2 minutes, (36.3±6.3)mmHg vs. (28.2±6.3)mmHg at 3 minutes, (40.1±7.1)mmHg vs. (30.5±6.2)mmHg at 4 minutes, (38.1±7.5)mmHg vs. (29.8±5.3)mmHg at 5 minutes; rSO₂: (45.4±5.2)% vs. (39.2±5.1)% at 1 minute, (47.2±3.6)% vs. (42.0±6.4)% at 2 minutes, (47.7±3.0)% vs. (41.5±5.4)% at 3 minutes, (47.0±2.5)% vs. (42.1±5.9)% at 4 minutes, (47.1±2.0)% vs. (41.5±7.4)% at 5 minutes; PETCO₂: (17.0±3.5)mmHg vs. (12.7±4.2)mmHg at 1 minute, (18.5±3.7)mmHg vs. (14.5±2.7)mmHg at 2 minutes, (20.7±5.3)mmHg vs. (15.5±3.2)mmHg at 3 minutes, (18.7±4.5)mmHg vs. (14.9±3.5)mmHg at 4 minutes, (18.2±3.2)mmHg vs. (14.5±4.2)mmHg at 5 minutes] (all P<0.05). The rate of ROSC was significantly higher in the ABO group than in the model group[100%(15/15) vs. 75%(9/12)] (P<0.05). Additionally, shorter duration of cardiopulmonary resuscitation, less number of shocks and lower doses of epinephrine were observed in the ABO group when compared with the model group[duration of cardiopulmonary resuscitation: 5(5, 5)minutes vs. 5(5, 12.5)minutes, number of shocks: 1(1, 1)times vs. 1(1, 4)times, dose of epinephrine: 0.62(0.62, 0.74)mg vs. 0.64(0.59, 2.59)mg] (all P<0.05). At 5 minutes after resuscitation, the level of arterial lactate was significantly decreased and the value of SjvO₂ was significantly increased in the ABO group compared with the model group[Lactate: (9.6±0.8)mmol/L vs. (10.8±1.4)mmol/L; SjvO₂: (50.0±8.6)% vs. (37.9±16.3)%] (both P<0.05). Conclusions In a swine model of TCA, ABO can increase cardiac and cerebral perfusion during cardiopulmonary resuscitation and improve the efficacy of cardiopulmonary resuscitation. It might provide a novel and effective method for the resuscitation of TCA in the clinical setting.

ObjectiveTo assess the level of internal exposure to PCP in a community population in Shanghai， to investigate the factors affecting the level of PCP， and to analyze the correlation between the exposure and thyroid hormone levels. MethodsA total of 464 residents of a community in Shanghai were selected as the study subjects. A questionnaire survey was conducted to obtain the demographic information， dietary situation， lifestyle and behavioral habits， and disease history of the individuals， and blood samples were collected. Gas chromatography-electron trap was applied to determine the PCP levels in serum. Multicategorical logistic regression analysis was used to analyze the possible influencing factors of PCP exposure in humans. Thyroid hormone levels were used as the dependent variable and serum PCP as the independent variable. Multiple linear regression analysis was used to assess the association between PCP and thyroid hormones in the community population after controlling the confounding factors such as age， gender， literacy， annual personal income， and chronic diseases. ResultsThe detection rate of serum PCP in 464 subjects was 90.3%， and the median serum PCP level was 0.43 μg·L^-1. The differences in PCP levels among different age groups were statistically significant. There were no significant differences in PCP levels among different gender and BMI groups. The study of PCP exposure factors showed that age， frequency of using plastic products， consumption of freshwater fish， type of occupation， annual income， and consumption of tea or coffee were the potential influencing factors for PCP exposure. Among them， age， frequency of using plastic products， consumption of tea or coffee， and consumption of freshwater fish were positively associated with PCP levels， and annual personal income was negatively associated with it. The results of multiple linear regression analysis showed that among men， PCP levels were positively correlated with TSH （b=0.105， 95%CI：0.017‒0.313） and negatively correlated with FT4 （b=-0.026， 95%CI：-0.057‒0.004）， and among women， PCP levels were positively correlated with TSH （b=0.092， 95%CI：-0.211‒0.904） and FT3 （b=0.017， 95%CI：-0.058‒0.230） and negatively correlated with FT4 （b=-0.013， 95%CI：-0.011‒0.037）. ConclusionSerum PCP detection is common among community residents in Shanghai. Different demographic characteristics or behavioral habits may increase or decrease PCP exposure. PCP exposure then affects human thyroid hormone levels.