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Objective:To investigate the characteristics of ischemic myocardial contracture after asphyxia-induced cardiac arrest (CA).Methods:Asphyxia and ventricular fibrillation (VF) induced cardiac arrest model was established. Thirty-one male Wistar rats were randomly(random number) assigned to the sham, asphyxia and VF groups. Electrocardiogram and blood pressure during CA stage were recorded. Arterial blood was drawn for blood gas analysis at 0 min after CA. The length and width of the heart were measured at 0,2,4,6 and 8 min after CA. The myocardial ATP contents were measured at 0 and 8 min after CA.Results:Compared with the VF group, the time of CA induction was longer in the asphyxia group[ (237±20 ) s vs (3±1) s, P<0.05]. At 0 min after CA, severe hypoxemia, carbon dioxide retention and acidosis had occurred in the asphyxia group, while these indexes in the VF group were basically normal. The length and width of the heart in the asphyxia group decreased gradually after CA, the myocardial contracture reached the limit around 6 min after CA, while the cardiac morphology of the VF group did not change significantly during the observation period of 8 min after CA. Myocardial ATP content in the asphyxia group decreased significantly at 0 min after CA ( P<0.05), while the difference between the VF group and the sham group was not statistically significant ( P>0.05). Conclusions:Myocardial contracture occurrs in the early stage of asphyxia CA, which may be related to ATP consumption in the asphyxia stage.
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Objective To investigate the neuroprotective mechanism of sevoflurane in rats resuscitated from cardiac arrest (CA).Methods A ventricular fibrillation-induced CA model was established.Forty Wistar rats were randomly divided into the sham group,sevoflurane group and control group.Apoptosis-related proteins were measured by Western blot at 24 h after restoration of spontaneous circulation (ROSC).The status of mitochondrial permeability transition pore (MPTP) were measured using a spectrophotometer,and the mitochondrial membrane potential (MMP) were measured with JC-1 fluorescent probe.At 72 h after ROSC,the apoptotic index of neurons in hippocampal CA1 region was counted by TUNEL staining.Results The protein expression of Bax,Bak,cleaved-caspase 9,cleavedcaspase 3 and cytosolic cytochrome c were lower in the sevoflurane group (all P＜0.05),the protein expression of Bcl-2 was higher in the sevoflurane group compared with the control group (P＜0.05).The sevoflurane group had a less opening status of MPTP and a higher MMP compared with the control group (all P＜0.05).The sevoflurane group had less apoptotic neurons compared with the control group (P＜0.05).Conclusion By up-regulating the expression of Bcl-2,down-regulating Bax and Bak,sevoflurane could reduce the apoptosis of neurons and decrease the opening of MPTP,eventually reduce cerebral injuries.
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Objective To investigate the characteristics of myocardial injury and its underlying mechanism in rats resuscitated from cardiac arrest. Methods Forty-two male Wistar rats were randomly(random number) assigned into the post-resuscitation (PR) 4 h, PR 24 h, PR 48 h, and sham groups. Ventricular fibrillation was induced by transcutaneous electrical epicardium stimulation and untreated for 6 min, followed by cardiopulmonary resuscitation (CPR). Myocardial function, glucose metabolism, myocardial ultrastructure, the status of mitochondrial permeability transition pore (MPTP) and mitochondrial membrane potential (MMP) were evaluated at different time points. Results Myocardial dysfunction was found at 4 h after restoration of spontaneous circulation (ROSC). The ejection fraction and cardiac output were decreased (all P<0.01), the diastole left ventricular posterior wall became thicker (P<0.01), and the end-diastolic volume was reduced (P<0.05). However, cardiac function was recovered almost completely at 48 h after ROSC. The PR 4 h group had a higher SUVmax, a more obvious decreased absorbance, and a lower MMP than the sham group (all P<0.01), but no statistically significant differences were noted between the PR 48 h group and the sham group (P>0.05). At 4 h and 24 h after ROSC, the mitochondria was swollen and the mitochondrial crista was sparse, but the myocardial ultrastructure was complete. Conclusions Post resuscitation myocardial dysfunction occurs after ROSC and the myocardial dysfunction is completely reversible at 48 h after ROSC, which may be related to the reversibility of myocardial injury and the gradual recovery of mitochondrial structure and function.
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Objective To determine the relationship between brain injury and cerebral glucose metabolism in rat model of cardiac arrest. Methods Asphyxia-induced cardiac arrest model was established. Forty-two male Wistar rats were randomly assigned to sham or experimental groups. Rats in the CA4,CA6 and CA8 group were treated with cardiopulmonary resuscitation(CPR) 4 min, 6 min and 8 min after cardiac arrest, respectively. The maximum standardized uptake value (SUVmax) of glucose was detected by PET, and neural defi cit score (NDS) were evaluated at 24 h and 72 h after ROSC. The numbers of injured neurons and apoptotic cells and the protein level of hexokinase I (HXK I) were measured at 72 h after ROSC. Results SUVmax, NDS and the level of HXK I were all decreased after ROSC, and interestingly, this declination of these markers was correlated with the prolongation of the duration of CA, the longer duration of CA the more declination of these biomarkers. Accordingly, the number of injured neurons and apoptotic cells increased were correlated with duration of CA, and thus CA8 group had greater numbers of those cells than CA6 group and CA4 group (P<0.05),and CA6 group had greater numbers of those cells than CA4 group(P<0.05). In addition, the SUVmaxwas positively correlated with NDS(P<0.05), and negatively correlated with the numbers of injured neurons and apoptotic index(P<0.05). Conclusions The degree of brain injury is associated with cerebral glucose metabolism, and PET may become a novel method to assess the severity of brain damage after CA.
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Objective To investigate the neurons autophagy and apoptosis after cerebral ischemia reperfusion (I/R) injury in mice,and to explore the effect of mild hypothermia on neurons autophagy and apoptosis.Methods The global cerebral ischemia-reperfusion injury model in C57 mice was established with carotid artery ligation method.Ninety-six C57 mice were randomly (random number) divided into 8 groups (n =12 in each group),namely control group (C0),sham group,normal body temperature group (NT,37 ℃) after I/R 6 h (C6 h),normal body temperature group after I/R 12 h (C12 h),normal body temperature group after I/R 72 h (C72 h),mild hypothermia group (MH,34 ℃) after I/R6 h (C6 h +MH),mild hypothermia group after I/R12 h (C12 h + MH),mild hypothermia group after I/R 72 h (C72 h + MH).The protein expressions of Sirt1,P-FoxO1,Rab7,P53 and autophagy related genes such as Beclin1,LC3 were detected by Western blot at given intervals.The LC3 granules were assayed by immunofluorescence.The neurons apoptosis was detected by TUNEL.The software of SPSS13.0 was used for statistical analysis.Measurement data was expressed with mean ± SD,and comparison between two groups was carried out with Student's t test,One-way ANOVA was used for comparisons among groups,and P ＜ 0.05 was considered statistically significant.Results The global cerebral ischemia-reperfusion injury model in C57 mice was established successfully with bilateral carotid arteries ligation method.Compared with the control group,the protein expressions of Sirt1,P-FoxO1,Rab7,Beclin1 and LC3 Ⅱ / Ⅰ were gradually reduced,especially at 12 h after I/R in NT group (P ＜ 0.05),while the expression of P53 was obviously increased (P ＜0.05).In MH group,the expressions of Sirt1,P-FoxO1,Rab7,Beclin1,LC3 Ⅱ / Ⅰ were higher than those in NT group (P ＜ 0.05).And the expression of P53 was lower than that in NT group (P ＜0.05).Immuno-fluorescence test showed that compared with the control group,the LC3 particles of neurons cells were decreased significantly in group C12 (at 12 h after I/R 6.0 ± 1.5 vs.18.1 ±2.5,P ＜0.05).Nevertheless,LC3 particles were increased in MH group compared with NT group (36.1 ± 4.5 vs.6.0 ± 1.5,P ＜ 0.05).The results of TUNEL test showed that compared with the control group,neurons cells apoptosis were significantly increased in C72 group (at 72 h after I/R,54.8％ ±7.5％ vs.5.5％ ±1.2％,P ＜ 0.05).However,compared with NT group,neurons apoptosis were decreased in MH group (28.8％ ±4.5％ vs.54.8％ ±7.5％,P＜0.05).Conclusions The neuron autophagy was significantly reduced and apoptosis was significantly increased after ischemia reperfusion injury (I/R) in mice.However,mild hypothermia could increase the expression of Sirt1,FoxO1,beclin1 and LC3,so as to promote neurons autophagy and reduce apoptosis,which would provide therapy target for neurons injury after hypoxia and provide soundly theoretical basis for mild hypothermia for clinical application.
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Objective To investigate the neurons autophagy and apoptosis after cerebral ischemia reperfusion (I/R) injury in mice,and to explore the effect of mild hypothermia on neurons autophagy and apoptosis.Methods The global cerebral ischemia-reperfusion injury model in C57 mice was established with carotid artery ligation method.Ninety-six C57 mice were randomly (random number) divided into 8 groups (n =12 in each group),namely control group (C0),sham group,normal body temperature group (NT,37 ℃) after I/R 6 h (C6 h),normal body temperature group after I/R 12 h (C12 h),normal body temperature group after I/R 72 h (C72 h),mild hypothermia group (MH,34 ℃) after I/R6 h (C6 h +MH),mild hypothermia group after I/R12 h (C12 h + MH),mild hypothermia group after I/R 72 h (C72 h + MH).The protein expressions of Sirt1,P-FoxO1,Rab7,P53 and autophagy related genes such as Beclin1,LC3 were detected by Western blot at given intervals.The LC3 granules were assayed by immunofluorescence.The neurons apoptosis was detected by TUNEL.The software of SPSS13.0 was used for statistical analysis.Measurement data was expressed with mean ± SD,and comparison between two groups was carried out with Student's t test,One-way ANOVA was used for comparisons among groups,and P ＜ 0.05 was considered statistically significant.Results The global cerebral ischemia-reperfusion injury model in C57 mice was established successfully with bilateral carotid arteries ligation method.Compared with the control group,the protein expressions of Sirt1,P-FoxO1,Rab7,Beclin1 and LC3 Ⅱ / Ⅰ were gradually reduced,especially at 12 h after I/R in NT group (P ＜ 0.05),while the expression of P53 was obviously increased (P ＜0.05).In MH group,the expressions of Sirt1,P-FoxO1,Rab7,Beclin1,LC3 Ⅱ / Ⅰ were higher than those in NT group (P ＜ 0.05).And the expression of P53 was lower than that in NT group (P ＜0.05).Immuno-fluorescence test showed that compared with the control group,the LC3 particles of neurons cells were decreased significantly in group C12 (at 12 h after I/R 6.0 ± 1.5 vs.18.1 ±2.5,P ＜0.05).Nevertheless,LC3 particles were increased in MH group compared with NT group (36.1 ± 4.5 vs.6.0 ± 1.5,P ＜ 0.05).The results of TUNEL test showed that compared with the control group,neurons cells apoptosis were significantly increased in C72 group (at 72 h after I/R,54.8％ ±7.5％ vs.5.5％ ±1.2％,P ＜ 0.05).However,compared with NT group,neurons apoptosis were decreased in MH group (28.8％ ±4.5％ vs.54.8％ ±7.5％,P＜0.05).Conclusions The neuron autophagy was significantly reduced and apoptosis was significantly increased after ischemia reperfusion injury (I/R) in mice.However,mild hypothermia could increase the expression of Sirt1,FoxO1,beclin1 and LC3,so as to promote neurons autophagy and reduce apoptosis,which would provide therapy target for neurons injury after hypoxia and provide soundly theoretical basis for mild hypothermia for clinical application.
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Objective To evaluate the effect of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) on survival and neurological function in adult patients with cardiac arrest.Methods The PubMed and Web of Science were searched to collect relevant literature from Jan 1980 to Nov 2015,and two reviewers strictly distinguished the studies,assessed the quality of studies and picked up the valuable data for statistical analysis by using RevMan 5.0.Results A total of 8 studies involving 27 18 patients were included in our review.Of them,462 patients were treated with ECPR and 2 256 patients were cared with CCPR.The meta analysis showed that the survival discharge rate (OR =2.92,95％ CI:2.24-3.81,P ＜ 0.01),long-term survival rate (OR =2.97,95％ CI:2.11-4.19,P＜0.01) and neurological function status (OR=3.50,95％CI:2.36-5.81,P＜ 0.01) of ECPR (n =182) were better than those of CCPR (n =182).In 4 studies,propensity score matching was used to minimize bias and heterogeneity.The meta analysis also showed that the rate of ROSC,survival discharge rate,long-term survival rate and neurological function status in ECPR were superior over CCPR.Conclusions ECPR would be the excellent measures to improve ROSC rate,survival discharge rate,long-term survival rate and neurological outcome in adult victims with cardiac arrest.
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AIM:To investigate the neuroprotective effect of hydrogen sulfide ( H2 S) after cardiopulmonary re-suscitation in rats with cardiac arrest ( CA) , and to explore the effects of H2 S on neuron autophagy.METHODS:The CA model was established through asphyxia.Male Wistar rats were randomly divided into sham group, model group and NaHS group.The levels of beclin-1 and LC3 II/I were measured by Western blot at 2 h, 4 h, 12 h and 24 h after the restoration of spontaneous circulation (ROSC).At 12 h after ROSC, the formation of autophagic vacuole with LC3 dots was deter-mined by immunohistochemical ( IHC) method.The phenomenon of neuron autophagy was observed under transmission electron microscope.The numbers of apoptotic neurons were counted by TUNEL staining at 72 h after ROSC.The neurolo-gic deficit score ( NDS) was used to evaluate the neurologic function after ROSC.RESULTS: The level of beclin-1 was gradually increased in model group, but it was increased and then gradually recovered in NaHS group ( P<0.05 ) .The conversion of LC3 II in the cerebral cortex was the same as beclin-1.The results of IHC showed that LC3-positive nuclei in model group were more than those in NaHS group ( P<0.05) .The number of autophagic vacuole in model group was more than that in NaHS group (P<0.05).The number of the TUNEL-positive cells in model group was more than that in NaHS group (P<0.05).The NDS of the animals in NaHS group after ROSC was lower than that in model group(P<0.05). CONCLUSION:H2 S inhibits neuronal autophagy, decreases apoptosis and improves neurologic function in CA rats after ROSC.
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AIM: To investigate the effect of cobalt chloride (CoCl2) on the apoptosis of neural stem cells (NSCs) and the expression of microRNA-26a (miR-26a) in vitro, and to explore the mechanisms of NSC apoptosis in-duced by CoCl 2 .METHODS:NSCs were exposed to CoCl 2 at different doses (200~600μmol/L) for 24 h.The cell via-bility and apoptosis were measured by CCK-8 assay and TUNEL method.The expression of miR-26a-3p, miR-26a-5p, GSK-3β, caspase-3, Bcl-2 and Bax was examined by real-time PCR.The protein levels of Bcl-2 and Bax were detected by Western blotting .RESULTS: The cell viability was inhibited and the apoptosis of NSCs was increased significantly by CoCl2 in a dose-dependent manner (P<0.05).CoCl2 at concentration of 400μmol/L for 24 h was used to induce apopto-sis and the expression of miR-26a was down-regulated compared with control (P<0.05).Exposure to CoCl2 at concentra-tion of 400μmol/L up-regulated the expression of GSK-3β, caspase-3 and Bax , down-regulated the expression of Bcl-2 and Bcl-2/Bax (P<0.05).CONCLUSION:CoCl2 at concentration of 400μmol/L induces the apoptosis of NSCs obviously . CoCl2 may induce the NSC apoptosis by mitochondrial apoptotic pathway .Declining miR-26a may be related to NSC apopto-sis.