Background:Anoxic brain injuries represent the main determinant of poor outcome after cardiac arrest(CA).Large animal models have been described to investigate new treatments during CA and post-resuscitation phase,but...Background:Anoxic brain injuries represent the main determinant of poor outcome after cardiac arrest(CA).Large animal models have been described to investigate new treatments during CA and post-resuscitation phase,but a detailed model that includes extensive neuromonitoring is lacking.Method:Before an electrically-induced 10-minute CA and resuscitation,46 adult pigs underwent neurosurgery for placement of a multifunctional probe(intracranial pressure or ICP,tissue oxygen tension or PbtO_(2) and cerebral temperature)and a bolt-based technique for the placement and securing of a regional blood flow probe and two sEEG electrodes;two modified cerebral microdialysis(CMD)probes were also inserted in the frontal lobes and accidental misplacement was prevented using a perforated head support.Result:42 animals underwent the CA procedure and 41 achieved the return of spontaneous circulation(ROSC).In 4 cases(8.6%)an adverse event took place during preparation,but only in two cases(4.3%)this was related to the neurosurgery.In 6 animals(13.3%)the minor complications that occurred resolved after probe repositioning.Conclusion:Herein we provide a detailed comprehensive neuromonitoring approach in a large animal model of CA that might help future research.展开更多
Objective： To analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion （I/R） injury. Metheds： Myocardial I/R injury model was constructed in mice by 30 min...Objective： To analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion （I/R） injury. Metheds： Myocardial I/R injury model was constructed in mice by 30 min of coronary occlusion followed by 24 h of reperfusion and pretreated with salvianolate 30 min before I/R （SAL group）. The SAL group was compared with SHAM （no I/R and no salvianolate）, I/R （no salvianolate）, and ischemia preconditioning （IPC） groups. Furthermore, an ERK1/2 inhibitor PD98059 （1 mg/kg）, and a phosphatidylinositol-3-kinase （PI3-K） inhibitor, LY294002 （7.5 mg/kg）, were administered intraperitoneal injection （i.p） for 30 min prior to salvianolate, followed by I/R surgery in LY and PD groups. By using a double staining method, the ratio of the infarct size （IS） to left ventricle （LV） and of risk region （RR） to LV were compared among the groups. Correlations between IS and RR were analyzed. Western-blot was used to detect the extracellular signal-regulated kinase 1/2 （ERK1/2） and protein kinase B （AKT） phosphorylation changes. Results： There were no significant differences between RR to LV ratio among the SHAM, I/R, IPC and SAL groups （P〉0.05）. The SAL and IPC groups had IS of 26.1% ± 1.4% and 22.3% ±2.9% of RR, respectively, both of which were significantly smaller than the I/R group （38.5% ± 2.9% of RR, P〈0.05, P〈0.01, respectively）. Moreover, the phosphorylation of ERK1/2 was increased in SAL group （P〈0.05）, while AKT had no significant change. LY294002 further reduced IS, whereas the protective role of salvianolate could be attenuated by PD98059, which increased the IS. Additionally, the IS was not linearly related to the RR （r=0.23, 0.45, 0.62, 0.17, and 0.52 in the SHAM, I/R, SAL, LY and PD groups, respectively）. Conclusion： Salvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.展开更多
Objective： To observe the in vivo effect of Danlou Tablet（丹蒌片,DLT） on myocardial ischemia and reperfusion（I/R） injury.Methods： DLT effects were evaluated in mouse heart preparation using 30-min coronary occlu...Objective： To observe the in vivo effect of Danlou Tablet（丹蒌片,DLT） on myocardial ischemia and reperfusion（I/R） injury.Methods： DLT effects were evaluated in mouse heart preparation using 30-min coronary occlusion followed by 24-h reperfusion and compared among sham group（n=6）,I/R group（n=8）,IPC group（ischemia preconditioning,n=6） and DLT group（I/R with DLT pretreatment for 3 days,750 mg·kg^（-1）·day^（-1）,n=8）.The effects of DLT were characterized in infarction size（IS） compared with risk region（RR） and left ventricle using the Evans blue/triphenyltetrazolium chloride double dye staining method in vivo.Furthermore,the dose-dependent effect of DLT on I/R injury was evaluated by double staining method.Five different concentrations of DLT（0.625,1.25,2.5,5 and 10 g·kg^（-1）·day^（-1）） were chosen in this study,and dose-response curve of DLT was obtained on these data.Results： The ratio of IS to left ventricle was significantly smaller in the DLT and IPC groups than the I/R group（P〈0.05 or P〈0.01）,the ratio of IS to RR was also reduced in the DLT and IPC groups（P〈0.01）,while there were no differences in RR among the four groups（P〉0.05）.Experiments showed incidence of arrhythmias was reduced in the DLT group（P〈0.01）.Furthermore,DLT produced a dose-dependent inhibitory effect with a half maximal inhibitory concentration of 1.225 g·kg^（-1）·day^（-1）.Conclusions： Our research concluded that DLT was effective in reducing I/R injury in mice,and provided experimental supports for the clinical use of DLT.展开更多
Background:Vascular inflow occlusion(VIO)during liver resections(Pringle manoeuvre)can be applied to reduce blood loss,however may at the same time,give rise to ischemia-reperfusion injury(IRI).The aim of this study w...Background:Vascular inflow occlusion(VIO)during liver resections(Pringle manoeuvre)can be applied to reduce blood loss,however may at the same time,give rise to ischemia-reperfusion injury(IRI).The aim of this study was to assess the characteristics of hepatic microvascular perfusion during VIO in patients undergoing major liver resection.Methods:Assessment of hepatic microcirculation was performed using a handheld vital microscope(HVM)at the beginning of surgery,end of VIO(20 minutes)and during reperfusion after the termination of VIO.The microcirculatory parameters assessed were:functional capillary density(FCD),microvascular flow index(MFI)and sinusoidal diameter(SinD).Results:A total of 15 patients underwent VIO;8 patients showed hepatic microvascular perfusion despite VIO(partial responders)and 7 patients showed complete cessation of hepatic microvascular perfusion(full responders).Functional microvascular parameters and blood flow levels were significantly higher in the partial responders when compared to the full responders during VIO(FCD:0.84±0.88 vs.0.00±0.00 mm/mm2,P<0.03,respectively,and MFI:0.69–0.22 vs.0.00±0.00,P<0.01,respectively).Conclusions:An interpatient heterogeneous response in hepatic microvascular blood flow was observed upon VIO.This may explain why clinical strategies to protect the liver against IRI lacked consistency.展开更多
基金Dr Annoni F.has been supported by the"Fonds Erasme pour la Recherche Médicale"for the entire length of the project.
文摘Background:Anoxic brain injuries represent the main determinant of poor outcome after cardiac arrest(CA).Large animal models have been described to investigate new treatments during CA and post-resuscitation phase,but a detailed model that includes extensive neuromonitoring is lacking.Method:Before an electrically-induced 10-minute CA and resuscitation,46 adult pigs underwent neurosurgery for placement of a multifunctional probe(intracranial pressure or ICP,tissue oxygen tension or PbtO_(2) and cerebral temperature)and a bolt-based technique for the placement and securing of a regional blood flow probe and two sEEG electrodes;two modified cerebral microdialysis(CMD)probes were also inserted in the frontal lobes and accidental misplacement was prevented using a perforated head support.Result:42 animals underwent the CA procedure and 41 achieved the return of spontaneous circulation(ROSC).In 4 cases(8.6%)an adverse event took place during preparation,but only in two cases(4.3%)this was related to the neurosurgery.In 6 animals(13.3%)the minor complications that occurred resolved after probe repositioning.Conclusion:Herein we provide a detailed comprehensive neuromonitoring approach in a large animal model of CA that might help future research.
基金Supported by National Natural Science Foundation of China(No.81473471 and No.81573708)Foundation of Guangdong Hospital of Chinese Medicine(No.YK2013B2N11,No.YN2014ZH01,and No.YN2014ZHR203)
文摘Objective： To analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion （I/R） injury. Metheds： Myocardial I/R injury model was constructed in mice by 30 min of coronary occlusion followed by 24 h of reperfusion and pretreated with salvianolate 30 min before I/R （SAL group）. The SAL group was compared with SHAM （no I/R and no salvianolate）, I/R （no salvianolate）, and ischemia preconditioning （IPC） groups. Furthermore, an ERK1/2 inhibitor PD98059 （1 mg/kg）, and a phosphatidylinositol-3-kinase （PI3-K） inhibitor, LY294002 （7.5 mg/kg）, were administered intraperitoneal injection （i.p） for 30 min prior to salvianolate, followed by I/R surgery in LY and PD groups. By using a double staining method, the ratio of the infarct size （IS） to left ventricle （LV） and of risk region （RR） to LV were compared among the groups. Correlations between IS and RR were analyzed. Western-blot was used to detect the extracellular signal-regulated kinase 1/2 （ERK1/2） and protein kinase B （AKT） phosphorylation changes. Results： There were no significant differences between RR to LV ratio among the SHAM, I/R, IPC and SAL groups （P〉0.05）. The SAL and IPC groups had IS of 26.1% ± 1.4% and 22.3% ±2.9% of RR, respectively, both of which were significantly smaller than the I/R group （38.5% ± 2.9% of RR, P〈0.05, P〈0.01, respectively）. Moreover, the phosphorylation of ERK1/2 was increased in SAL group （P〈0.05）, while AKT had no significant change. LY294002 further reduced IS, whereas the protective role of salvianolate could be attenuated by PD98059, which increased the IS. Additionally, the IS was not linearly related to the RR （r=0.23, 0.45, 0.62, 0.17, and 0.52 in the SHAM, I/R, SAL, LY and PD groups, respectively）. Conclusion： Salvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.
基金Supported by Guangdong National Scientific Funding(No.2014A030313402)Guangdong Medical Research Foundation(No.A2014271)National Natural Science Foundation of China(No.81473471 and No.81573708)
文摘Objective： To observe the in vivo effect of Danlou Tablet（丹蒌片,DLT） on myocardial ischemia and reperfusion（I/R） injury.Methods： DLT effects were evaluated in mouse heart preparation using 30-min coronary occlusion followed by 24-h reperfusion and compared among sham group（n=6）,I/R group（n=8）,IPC group（ischemia preconditioning,n=6） and DLT group（I/R with DLT pretreatment for 3 days,750 mg·kg^（-1）·day^（-1）,n=8）.The effects of DLT were characterized in infarction size（IS） compared with risk region（RR） and left ventricle using the Evans blue/triphenyltetrazolium chloride double dye staining method in vivo.Furthermore,the dose-dependent effect of DLT on I/R injury was evaluated by double staining method.Five different concentrations of DLT（0.625,1.25,2.5,5 and 10 g·kg^（-1）·day^（-1）） were chosen in this study,and dose-response curve of DLT was obtained on these data.Results： The ratio of IS to left ventricle was significantly smaller in the DLT and IPC groups than the I/R group（P〈0.05 or P〈0.01）,the ratio of IS to RR was also reduced in the DLT and IPC groups（P〈0.01）,while there were no differences in RR among the four groups（P〉0.05）.Experiments showed incidence of arrhythmias was reduced in the DLT group（P〈0.01）.Furthermore,DLT produced a dose-dependent inhibitory effect with a half maximal inhibitory concentration of 1.225 g·kg^（-1）·day^（-1）.Conclusions： Our research concluded that DLT was effective in reducing I/R injury in mice,and provided experimental supports for the clinical use of DLT.
文摘Background:Vascular inflow occlusion(VIO)during liver resections(Pringle manoeuvre)can be applied to reduce blood loss,however may at the same time,give rise to ischemia-reperfusion injury(IRI).The aim of this study was to assess the characteristics of hepatic microvascular perfusion during VIO in patients undergoing major liver resection.Methods:Assessment of hepatic microcirculation was performed using a handheld vital microscope(HVM)at the beginning of surgery,end of VIO(20 minutes)and during reperfusion after the termination of VIO.The microcirculatory parameters assessed were:functional capillary density(FCD),microvascular flow index(MFI)and sinusoidal diameter(SinD).Results:A total of 15 patients underwent VIO;8 patients showed hepatic microvascular perfusion despite VIO(partial responders)and 7 patients showed complete cessation of hepatic microvascular perfusion(full responders).Functional microvascular parameters and blood flow levels were significantly higher in the partial responders when compared to the full responders during VIO(FCD:0.84±0.88 vs.0.00±0.00 mm/mm2,P<0.03,respectively,and MFI:0.69–0.22 vs.0.00±0.00,P<0.01,respectively).Conclusions:An interpatient heterogeneous response in hepatic microvascular blood flow was observed upon VIO.This may explain why clinical strategies to protect the liver against IRI lacked consistency.
