1.Short period of mild hypothermia improves resuscitation outcome in a porcine model of prolonged ventricular fibrillation
Heng LI ; Zhengfei YANG ; Zitong HUANG ; Yongqin LI ; Tao YU
Chinese Journal of Emergency Medicine 2016;25(1):22-27
Objective To investigate the resuscitation outcome after a short period of mild hypothermia in porcine model of prolonged ventricular fibrillation (VF).Methods Fourteen male healthy domestic swine weighting 34 to 36 kg were used.VF was induced electrically and maintained untreated for 11 mins,followed by manual cardiopulmonary resuscitation (CPR) procedure.Two investigators initiated chest compression and bag-valve mask ventilation in pattern of 2 min rotation.A biphasic wave of 120 J electric defibrillation (ED) was attempted 6 mins after CPR.If there was no return of spontaneous circulation (ROSC),CPR was restored and ED was delivered when necessarily.Resuscitation was considered unsuccessful if absence of ROSC for 12 mins.However,if ROSC occurred,animals were randomly (random number) diveded into normothermia (NT) group and hypothermia treatment (CH) group.Animals in CH group were immediately cooled by using intravenous infusion of ice-cold saline and surface cooling.Core temperature was reduced to 32-34 degrees centigrade within 120 mins and maintained at this level for 2 h.Active rewarming was completed within 2 h until baseline body temperature was reached.Data of hemodynamic variables,blood-gas analysis and blood lactate before VF of two groups were recorded.Meawhile,cardiac output (CO),heart rate and Tc after ROSC were recorded.Neurological defect scores (NDS) were evaluated every 24 h until 96 h after ROSC.Variables were compared using either Fisher test or repeated measures analysis of variance,followed by Bonferroni for multiple comparisons.A two-sided P value <0.05 was regarded statistically significant.Results There was no significant difference in body weight,mean arterial pressure,CO,pH,pressure of end-tidal carbon dioxide (ETCO2) and lactate between groups before VF.In the period of CPR,there were also no significant difference in total resuscitation time,first shock success rate,ROSC rate,shock ROSC rate,total number of shock and doses of epinephrine.However,animals in CH group survived longer time than that in NT groups [(96.00 ± 0.00) hvs.(49.71 ±43.65) h,P=0.031].Meanwhile,the survival rate of 96 h was significantly higher in CH than that in NT (P < 0.05).For neurological function,there was a obviously better NDS in CH group than that in NT group within ROSC 96 h (P < 0.05).Conclusion Even a short duration of 2 hour mild hypothermia could improve resuscitation outcome in porcine model of 11 minute VF.
2.Protective role of heme oxygenase in myocardial dysfunction postresuscitation
Xiaohong WANG ; Xiangshao FANG ; Zitong HUANG ; Yue FU ; Wenjing LI
Chinese Journal of Emergency Medicine 2009;18(4):380-385
Objective To study the cardioprotection effects of heme oxygenase-1(HO-1)on cardiopulmonary resuscitation(CPR).Method Male Sprague-Dawley rats were asphyxiated for 9 minutes and resuscitated.Rats wefe randomly divided into 4 groups,namely,sham asphysiation group,CPR group,Hemin group and Heroin +ZnPP group(zinc protoporyphyrin IX).Resuscitated groups were further divided into two subgroups according to various intervals:6 hours and 24 hours after resuscitation.Hemodynamic was observed.Serum creatine phosphokinase-MB(CPK-MB)and lactate dehydrogenase were determined.HO-1 in heart tissue homogenates was assayed.Ultrastructure of rats hearts was examined.Statical evaluation was performed with analysis of variance.Results The mean blood pressure(MBP)in resuscitated groups was significantly reduced after resuscitation,hadn't any difference between supgroups.The scores of dp/dt 40 and-dp/dt were significantly decreased in CPR group and Hemin+ZnPP group after resuscitation(all P<0.05),but dP/dt40 in Heroin group did nol differ significantly after resuscitation.and-dp/dt decreased only 0.5 hours and one hour after resuscitation and returned to baseline values two hours after resuscitation.The scores of dp/dt 40and-dp/dt in Heroin group at different intervals after resuscitation were significantly higher than those in CPR group and Hemin+ZnPP group(all P<0.05).Serum CPK-MB and LDH in CPR group and Hemin+ZnPP group at 6 hours and 24 hours after resuscitation were significantly higher than those in Hemin group(all P<0.05).The cardiac tissue ultrastructure of rats in Hemin group was more intact than that of CPB group and Hemin+ZnPP goup.HO-1 levels in heart tissue homogenates of Hemin group at 6 hours and 24 hours after resuscitation were significantly higher than those in CPR group and Heroin+ZnPP group(all P<0.05).Conclusions HO-1 expression induced by Heroin can effectively improve post-resuscitation myocardial dysfunction,alleviate cardiac injury,keep the ultrassructure integrity of cardiac myocytes.It may be a new approach to treat myocardial dysfunction after resuscitation.
3.The mobilization of stem cells promote the recovery of the ischemia brain injury after cardiopulmonary resuscitation
Jun ZHU ; Maoqin LI ; Xiangshao FANG ; Zitong HUANG
Chinese Journal of Emergency Medicine 2015;24(1):22-27
Objective To explore the therapeutic potential and mechanism of stem cells mobilized by granulocyte colony-stimulating factor (G-CSF) and AMD3100 to repair global cerebral ischemia injuries in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR).Methods Cardiac arrest was induced by asphyxia.Fifty-six SD rats were randomly assigned into four groups:G-CSF group,G-CSF + AMD3100 group,CPR control group and sham operated group.The animals were sacrificed at 3d and 6d after CPR respectively.The neurological status and morphological changes of damaged cerebrum,the apoptosis of nerve cells and vascular endothelial growth factor (VEGF) expressed in brain tissue and capillary density in hippocampus and temporal lobe cortex were measured and analyzed by means of neurological deficit score (NDS),adhesive tape removal test (TRT),ELISA,MRI and immunofluorescence.Results NDS in G-CSF + AMD3100 group (61.4 ± 10.7) was significantly higher than that in CPR control group (49.9 ± 10.4) at 3 d after CPR (P <0.05).And less time consumption for TRT found in G-CSF + AMD3100 group (85.5 ±28.9) s rather than was in CPR control group (148.1 ± 23.8) s and G-CSF group (118.5 ± 30.4) s (P < 0.05).The severity of cerebral injury assessed by MRI was significantly milder at both 3 d and 6 d in the two stem cell mobilization groups.The apoptosis rate of nerve cells in G-CSF + AMD3100 group (0.23 ± 0.06) was significantly lower than that in G-CSF group (0.34 ±0.08) at 3 d after CPR,and that in both stem cell mobilization groups was lower than that in CPR control group (0.44 ± 0.09) (P < 0.05).At 3 d and 6 d after CPR,the levels of VEGF in brain tissue were (106.2 ±23.3) pg/mL and (79.9 ± 18.4) pg/mL in G-CSF + AMD3100 group,and were (50.6 ± 13.7) pg/mL and (73.9 ± 16.6) pg/mL in G-CSF group,which were both significantly higher than that in CPR control group (23.1 ± 10.2) pg/mL and (36.2 ± 12.8) pg/mL (P <0.05).At 3 d after CPR,the cerebral capillary density (351.8 ±67.9) branches in every high power field (A/HPF) was significantly higher in G-CSF + AMD3100 group than that (301.4 ± 77.3) A/HPF in G-CSF group and (250.4 ± 48.0) A/HPF in CPR control group (P < 0.05).The cerebral capillary density in G-CSF group elevated to (348.4 ±76.7) A/HPF at 6 d after CPR which was significantly higher than that at 3 d (P <0.05),and there was no difference between that at 3 d and 6 d in G-CSF + AMD3100 group.Conclusions The mobilization stem cells improve the impaired neurological function.The increased expression of VEGF in brain tissue,the neo-vascularization promoted by the mobilized stem cells and the inhibition of nerve cell apoptosis may be associated with the protective effects of the stem cell mobilization.
4.Effects of mitochondrial division inhibitor on neurological function and neuronal apoptosis in rats after cardiopulmonary resuscitation
Yi LI ; Peng WANG ; Jiali LIN ; Zitong HUANG
Chinese Critical Care Medicine 2015;27(12):950-954
Objective To investigate the effects of mitochondrial division inhibitor 1 (mdivi-1) in rats after cardiopulmonary resuscitation (CPR) and its mechanism.Methods Fifty Sprague-Dawley (SD) rats were randomly (random number table) divided into sham group (n =8),cardiac arrest (CA) model group (n =14),dimethyl sulfoxide post-treatment control group (DMSO group,n =14),and mdivi-1 post-treatment group (mdivi-1 group,n =14).Asphyxial CA was reproduced in animals,and they were resuscitated by CPR.In the mdivi-1 group or DMSO group,the animals were given mdivi-1 (1.2 mg/kg) or DMSO (0.1%) intravenously after restoration of spontaneous circulation (ROSC).The neurological functions were assessed using neurological deficit score (NDS) determined at 24,48 and 72 hours after CPR.The brain tissues were harvested at 72 hours after CPR.The histopathologic changes were assessed by hematoxylin and eosin (HE) staining,and the normal neuron was counted.The neuronal apoptosis was assessed with terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining,and the expressions of cytochrome C (Cyt-C) protein in mitochondria and cytoplasm from hippocampus were determined by Western Blot.Results NDS in all experiment groups was gradually increased after CPR,and they were significantly lower than thoseo.f the sham group at 24,48,and 72 hours (51.5±3.7 vs.80.0±0.0,59.3±3.6 vs.80.0±0.0,66.7±2.6 vs.80.0±0.0,all P < 0.05).The number of normal pyramidal neurons in the hippocampal CA1 region was markedly reduced (cells/HP:4.4± 1.1 vs.23.1 ± 4.0,P < 0,05),the apoptotic index was significantly increased [(86.9 ± 6.9)% vs.(3.4 ± 0.8)%,P < 0.05],the expressions of Cyt-C in mitochondria were significantly decreased (A value:0.46±0.18 vs.1.00±0.00,P < 0.05),and the expressions of Cyt-C in cytoplasm were significantly up-regulated (A value:6.65±0.21 vs.1.00±0.00,P < 0.05).Compared with the CA group,NDS at 24 hours and 48 hours in mdivi-1 group was slightly increased (55.2 ± 3.3 vs.51.5 ± 3.7,64.7 ± 2.4 vs.59.3 ± 3.6,both P > 0.05),and it was significantly increased at 72 hours (74.5±2.3 vs.66.7 ± 2.6,P < 0.05),the number of normal pyramidal neurons in the hippocampal CA1 region was markedly increased (cells/HP:16.2±2.4 vs.4.4± 1.1,P < 0.05),the apoptotic index was dramatically reduced [(42.3 ± 3.9)% vs.(86.9 ± 6.9)%,P < 0.05],the expressions of Cyt-C in mitochondria were significantly increased (A value:0.83 ± 0.22 vs.0.46 ± 0.18,P < 0.05),and the expressions of Cyt-C in cytoplasm were significantly decreased (A value:3.84±0.47 vs.6.65±0.21,P < 0.05).There was no statistically significant difference in above indexes between CA group and DMSO group.Conclusion By inhibiting mitochondrial Cyt-C apoptotic pathway to reduce neuronal apoptosis in rats after CA-CPR,mdivi-1 can improve brain function after CPR.
5.Prophylactic intra-aortic balloon pump implantation in patients with high-risk coronary artery disease in percutaneous coronary intervention
Zitong GUO ; Xin SHEN ; Yesai MU ; Guoqing LI
Chinese Journal of Interventional Cardiology 2017;25(5):266-270
Objective To evaluate the feasibility and therapeutic efficacy of prophylactic implantation of intraaortic balloon pump in patients with high-risk coronary artery disease.Methods 121 patients with high-risk coronary heart disease who received prophylactic implantation of intraaortic balloon pump in percutaneous coronary intervention were enrolled as the treatment group (Group A),and another 119 patients with high-risk coronary heart disease who had conventional coronary intervention were enrolled as the control group (Group B).The rates of intraoperative malignant arrhythmia (ventricular tachycardia,ventricular fibrillation),acute left heart failure,cardiogenic shock and sudden death were compared between the two group.NT-proBNP levels,left ventricular systolic function and the rates of major adverse cardiac events,within 30 days of PCI and after 1 year were compared between the two groups.Results The event rates of intraoperative malignant arrhythmia,acute left heart failure,cardiogenic shock,and sudden death in Group A was significantly lower than those in Group B (all P < 0.05).Postoperative hematoma were found in 2 cases,aortic dissection in 1 case and thrombocytopenia in 1 case in Group A without significant difference as compared to Group B (P > 0.05).Within 30 days after PCI,NT-proBNP levels and left ventricular diastolic diameter in Group A were lower than those in Group B while the left ventricular ejection fraction in Group A was higher than that in Group B (all P < 0.05).The rates of major cardiac adverse events,including sudden cardiac death and severe heart failure were lower than those in Group B (all P < 0.05).At 1 year after PCI,the NT-proBNP levels left ventricular diastolic diameter in Group A were lower than those in Group B with the left ventricular ejection fraction in Group A was higher than that in Group B (all P < 0.05).There were no significant differences in the rates of major cardiac adverse events,including sudden cardiac death and severe heart failure after 1 year(all P > 0.05).Conclusions For patients with high-risk coronary heart disease undergoing coronary intervention,prophylactic implantation of intraaortic balloon pump may decrease the incidence of intraoperative complications,reduce the incidence of cardiac death and severe heart failure within 30 days,and improve the left ventricular function after 1 year.Its role in reducing long term major cardiac adverse events after 1 year still needs more clinical trials for funther justification.
6.Preliminary observation of the expressions of SOCS-1 and SOCS-3 in myocardium of patients with sudden cardiac death
Liang CHEN ; Zhongfu MA ; Hao TANG ; Yanbing LIANG ; Zhibin CHEN ; Zhenyu LI ; Zitong HUANG ; Longyuan JIANG
Chinese Journal of Emergency Medicine 2010;19(3):277-280
Objective To investigate the expressions and clinical significanees of suppressors of cytokine signaling-1 (SOCS-1) and SOCS-3 in myocardium of patients with sudden cardiac death (SCD). Method This study included myocardial autopsy specimens of 24 patients admitted between 2005 and 2006. Of them, 9 cases had the findings of autopsy examination consistent with coronary atberosclerosis (non-myocardial infarction) leading to SCD (non-MI group), 7 patients died of acute myocardial infarction (MI group) and 8 patients died of traffic accidents and trauma The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the myocardium of non-MI and con-trol group were detected by using RT-PCR. The levels of SOCS-1 protein and SOCS-3 protein were detected by us-ing immunohistochemistry. Statistical analysis were performed by using SPSS version 13.0 software and the data were processed with ANOVA test. Results The expressions of SOCS-1 mRNA and SOCS-3 mRNA in non-MI and MI groups were were significantly higher than those in control group (0. 788±0. 101) and (0. 741±0.111) vs.(0.436±0.044) (P <0.01); (0.841±0.092) and (0.776±0.070) vs.(0.454±0.076), P <0.01, re-spectively). The antibody-positive cells of SOCS-1 protein in myocardium of non-MI group and MI group were significantly higher than those in myoeardium of control group (320.00±48.48) and (347.14±70.88) vs.(42.50±10.35) (P < 0.01), respectively. The antibody-positive cells of SOCS-3 protein in myoeardium of non-MI group and MI group were significantly higher than those in myocardium of control group (381.11±59.25) vs.(40.00±10.69), (P < 0.01)and (332.86±111.91) vs. (40.00±10.69), (P =0.001). Conclusions The expressions of SOCS rnRNA and SOCS-3 mRNA in myoeardium of patients with SCD from coronary diseases are significantly increased contributing to the pathogenesis of SCD.
7.Comparison of cardiac arrest induced by ventricular fibrillation or induced by asphyxia in rats
Jun ZHU ; Xiangshao FANG ; Yue FU ; Jun JIANG ; Heng LI ; Jiakang LIANG ; Zitong HUANG
Chinese Journal of Emergency Medicine 2011;20(1):14-19
Objective To compare the changes of physiological parameters after cardiac arrest caused by asphyxia with that of cardiac arrest induced by ventricular fibrillation in rats and assess the values of the parameters on predicting ROSC and 24 h survival rate. Method Two groups of Sprague-Dwaley rats, which randomly (ramdom number) included 30 animals in each group, were investigated. Cardiac arrest were induced by asphyxia (AS group) or ventricular fibrillation(VF group). PETCO2, aortic pressure, left ventricular pressure and ECG of limb lead Ⅱ were recorded continuously, dP/dt4o was calculated with the windaq software. The parameters were compared between the two groups at baseline, precordial compression(PC) 10 s, PC 1 min, PC 3 min, ROSC 1 h and ROSC 2 h. The relations were explored between the parameters and ROSC/24 h survival rate. Results PETCO2,aortic pressure, left ventricular pressure and ECG have distinctive changes in the two groups. In group VF, PETCO2 of ROSC rats at BL, PC 1 min and PC 3 min were higher than those of Non-ROSC rats (P < 0.05); PETCO2of 24 h survival rats at ROSC 1 h and ROSC 2 h were higher than those of 24 h death rats (P < 0.05), which were not observed in the group AS. dP/dt40 and - dP/dt40 at ROSC 1 h and ROSC 2 h in group VF were higher than those in group AS (P < 0.05). Conclusions Physiological parameters after cardiac arrest caused by asphyxia or that of cardiac arrest induced by ventricular fibrillation in rats have unique features respectively. PETCO2 in cardiac arrest caused by ventricular fibrillation may predict ROSC and 24 h survival rate. Researchers have to select the appropriate cardiac arrest model according their research purposes and clinical requirments.
8.Exploration of Variety of Matrix Metalloproteinase 9 and Blood Brain Barrier in Cardiopulmonary Resuscitation Rats
Zhijie HE ; Zijun ZOU ; Yun ZHANG ; Minggen ZHOU ; Zuyong LI ; Xiangshao FANG ; Zitong HUANG
Journal of Sun Yat-sen University(Medical Sciences) 2009;30(4):418-421,427
[Objective] To explore the variety of matrix metalloproteinase 9 (MMP9) and blood brain barrier (BBB) in cardiopulmonary resuscitation rats.[Methods] Eighty rats were randomly divided into 2 groups:the sham-operated group (n = 40) and the resuscitation group (n = 40).The two groups were anaesthetized and endotracheally intubated,the resuscitation group was also induced to cardiac arrest by aphysia.Then the rats were put to death and samples were taken at immediate,3 h,9 h,24 h,and 48 h.After that,the expression of MMP9,MMP9 mRNA,water content and Evans blue content in brain tissue were detected.Ultramicrostructure of brain tissue was observed with electron microscope.[Results] Compared to the sham-operated group,at 3 h,9 h,24 h and 48 h,the expression of MMP9 of resuscitation group was significantly changed.MMP9mRNA significantly increased.Water content statistically increased and so was Evans blue content.The change of ultramicrostructure in the resuscitation group at 3 h,9 h,24 h,and 48 h was obvious.[Conclusion] The expression of MMP9 and MMP9mRNA obviously increased in the cerebral ischemia model with CPR rats,and got to peak at 24 h.Water content and Evans blue content in brain tissue obviously increased in the cerebral ischemia model with CPR rats,BBB was destroyed,and the peak was 24 h.The injury of ultramicrostructure of brain tissue with electron microscope was obvious,and the peak was 24 h.
9.Anti-inflammatory and Anti-allergic Effects of Qifangbimin Particle
Yan XU ; Huilun CHU ; Deming KONG ; Zitong DING ; Qinqin GAO ; Yue YAN ; Wenyan SUN ; Youlin LI
China Pharmacist 2017;20(5):816-819
Objective: To research the anti-inflammatory and anti-allergic effects of Qifangbimin particle.Methods: The anti-inflammatory effects were observed by the methods of xylene-induced ear-swelling in mice and cotton-ball induced granuloma in rats.The anti-allergic effects were evaluated by the method of passive skin allergy model in rats and ear-heterogeneous passive skin allergy model in mice.Results: In the treatment groups with Qifangbimin particle, the swelling degree of ear edema induced by dimethylbenzene in mice was significantly suppressed when compared with that in the control groups (P<0.01 or 0.05) , however, the particle had no significantly inhibitory effect on granulation tissue hyperplasia induced by cotton-ball in rats.The Qifangbimin particle groups obviously decreased the absorbance value of locus coeruleus on rats' back (P<0.01 or 0.05), and Qifangbimin particle at high dose significantly reduced the absorbance value of locus coeruleus of auricle in mice (P<0.01 or 0.05).Conclusion: Qifangbimin particle has significant anti-inflammatory and anti-allergic effects.
10.The differences in brain damage between asphyxial nd ventricular fibrillation cardiac arrests
Qingming Lin ; Shen Zhao ; Heng Li ; Xiangshao Fang ; Yue Fu ; Lili Zhou ; Zitong Huang
Neurology Asia 2013;18(3):303-309
Objective: Asphyxia and ventricular fibrillation are the two most prevalent causes of cardiac arrest. The
study investigated the differences in brain damage after cardiac arrest between asphyxial and ventricular
fibrillation cardiac arrests in rats. Methods: Male healthy Sprague-Dawley rats were randomly assigned
to the asphyxial group (cardiac arrest of 6 min, n=15), ventricular fibrillation group (cardiac arrest of
6 min, n=15) and sham group (n=5). Neurologic deficit scores and tape removal test were evaluated
at 1, 3 and 7 days after cardiopulmonary resuscitation from three groups. Serum S-100B and brain
histopathologic damage scores were also examined. Results: There were no differences in neurologic
performance at 1, 3 and 7 days after cardiopulmonary resuscitation between the asphyxial group and
ventricular fibrillation group (P>0.05, respectively). Serum S-100B level was higher in the asphyxial
group at 1, 3 and 7 days, compared with the ventricular fibrillation group (P<0.05, respectively). There
were significantly higher histopathologic damage scores at 1, 3 and 7 days in the asphyxial group
compared with the ventricular fibrillation group (P<0.05, respectively).
Conclusion: Asphyxial cardiac arrest has worse morphologic brain damage compared with ventricular
fibrillation cardiac arrest, but the functional brain damage caused by asphyxial cardiac arrest is similar
to that caused by ventricular fibrillation cardiac arrest.