Study on the mechanism of resolvin D1 in alleviating brain injury after cardiopulmonary resuscitation through the inhibition of autophagy in pigs北大核心CSCD

Objective To investigate the mechanism of resolvin D1 (RvD1) in alleviating brain injury after cardiopulmonary resuscitation (CPR) through regulating autophagy pathway in pigs. Methods Nineteen male domestic pigs, weighing 30-41 kg, were divided into 3 groups using a random number table method: sham group (S group, n=5), CPR group (n=7), and RvD1 group (n=7). In the S group, the animals only experienced general preparation. In the CPR and RvD1 groups, the pig CPR model was established by 8 min of cardiac arrest caused by electrically induced ventricular fibrillation, and followed by 5 min of CPR. At 5 min after resuscitation, a dose of 0.6 μg/kg of resolvin D1 was injected via femoral vein in the RvD1 group, and the same amount of vehicle was similarly administered in the other two groups. At 1, 3, 6, and 24 h after resuscitation, blood samples were collected from the femoral vein to measure serum concentrations of neuron specific enolase (NSE) and S100β protein by ELISA. At 24 h after resuscitation, neurological function was evaluated by neurological deficit score (NDS), and then the animals were euthanized to obtain cerebral cortex for measuring the expressions of phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated mammalian target of rapamycin (p-mTOR), microtubule-associated protein light chain 3 (LC3 II) and p62 by Western blot. The variables were compared with One-way analysis of variance and then the Bonferroni test among the three groups. Results During 24 h after resuscitation, the NDS was significantly increased accompanied with significantly greater concentrations of NSE and S100β in serum in the CPR and RvD1 groups compared to the S group (all P<0.05). However, the NDS was significantly decreased at 24 h after resuscitation [(182±34) vs.(124±18), P<0.05], and serum NSE and S100β were significantly reduced starting 3 h after resuscitation in the RvD1 group compared to the CPR group [NSE (ng/mL): (23.1±3.8) vs. (18.0±2.2) at 3 h, (27.3±2.9) vs. (19.8±1.4) at 6 h, and (28.1±1.3) vs. (15.1±2.1) at 24 h; S100B (pg/mL): (1 611±208) vs. (1 322±100) at 3 h, (1 825±197) vs. (1 410±102) at 6 h, and (1 613±138) vs. (1 183±139) at 24 h, all P<0.05]. The expression levels of p-AMPK and LC3 II were significantly increased while the expression levels of p-mTOR and p62 were significantly decreased at 24 h after resuscitation in the CPR and RvD1 groups compared to the S group (all P<0.05). However, the expression levels of p-AMPK and LC3 II were significantly lower and the expression levels of p-mTOR and p62 were significantly higher at 24 h after resuscitation in the RvD1 group compared to the CPR group [p-AMPK: (0.28±0.08) vs. (0.17±0.03); LC3 II: (0.33±0.09) vs. (0.21±0.04); p-mTOR: (0.13±0.02) vs. (0.16±0.02); p62: (0.16±0.05) vs. (0.22±0.02), all P<0.05]. Conclusions The protective mechanism by which RvD1 alleviates brain injury after CPR in pigs might be related to the inhibition of neuronal autophagy mediated by AMPK/mTOR pathway. © 2022 Chinese Medical Association. All rights reserved.     

Comparison of myocardial metabolism by using PET after resuscitation between ventricular fibrillation cardiac arrest and asphyxia cardiac arrest北大核心CSCD

Objective To characterize myocardial metabolism using positron emission tomography (PET) in porcine models of ventricular fibrillation cardiac arrest (VFCA) and asphyxiation cardiac arrest (ACA) after resuscitation. Methods Thirty-Two healthy miniature pigs were randomized into two groups. The pigs of VFCA group (a = 16) were subject to programmed electric stimulation to create a ventricular fibrillation cardiac arrest, and the pigs of ACA group (n = 16) were subjected to endotracheal tube clamping to establish a cardiac arrest (CA). Once modeling was established, pigs with CA were left untreated for a period of 8 mm. Two minutes following initiation of cardiopulmonary resuscitation (CPR), defibrillation was attempted until the restoration of spontaneous circulation (ROSC) was achieved or animals died. To assess myocardial metabolism, PET was performed before modeling, 4 hrs and 24hrs after ROSC. To analyze 18F-FDG myocardial uptake in PET, the maximum standardized uptake value (SUV1) was measured. Results ROSC was obtained in 100% of pigs in VFCA group and only 50% in ACA group. The average survival time in VFCA pigs was significantly longer than that in ACA pigs (22. 63 ± 0. 95) hvs. (8. 75 ± 2. 54) h, P <0.01. VFCA pigs had better mean arterial pressure and cardiac output after ROSC than ACA pigs. Myocardial metabolism imaging using PET demonstrated that myocardial metabolism injuries after ACA were more severe and widespread than those after VFCA at 4 hrs and 24hrs after ROSC and SUV> was much higher in VFCA group than that in ACA group [4 h after ROSC: (1.9 ± 0. 3) vs. (1.0 ±0.4), P <0. 01; 24 h after ROSC: (2.4 ±0.6) vs. (1.2±0.5), P <0.01]. Conclusions Compared with VFCA, ACA causes more severe cardiac metabolism dysfunction associated with less successful resuscitation and shorter survival time; therefore they should he treated as different pathological entities.     

Effect of dopamine on hemodynamics and cerebral oxygen metabolism in the early stage-of post-resuscitation in rabbit with cardiac arrest北大核心CSCD

Objective To observe the effects of dopamine in different doses on hemodynamics and cerebral oxygen metabolism in the early stage of post-resuscitation in rabbit with cardiac arrest. Methods Healthy adult rabbits were randomly(random number) divided into 4 groups according to the different doses of dopamine administration: control group (CG), low dose group (LG), medium dose group (MG), high dose group (HG), (n=15 in each group). Ventricular fibrillation (VF) was induced by electricity and cardiopulmonary resuscitation (CPR) was performed subsequently as the experiment designed. When 10 rabbits with restoration of spontaneous circulation (ROSC) were got each group, it was enough for experiment carried out. Cardiac output (CO), mean arterial pressure (MAP), heart rate (HR), systemic vascular resistance index (SVRI) and the cerebral local tissue blood oxygen saturation (TOI) were observed at 0 min, 15 min, 30 min, 60 min, 120 min after ROSC. The animals were sacrificed at 120 min after ROSC, brain tissues were harvested for study by using HE staining. Repeated measure analysis of variance was used to determine the statistical significance among the four groups at different intervals. Multi-group quantitative data was analyzed by one way ANOVA and then further by LSD test for multiple comparisons. Chi-square test or Fisher's exact probabilities was applied for multi-group binomial classification variable. Log-rank test was used for comparisons of survival curves in four groups. A two-tailed value of P<0.05 was considered statistically significant. Results There were no differences in the rate of ROSC among groups. Compared with CG and LG, ROSC time was shorter in MG (27715 vs. 19012, PO.01 ; 25216 vs. 19012, P=0.016 ) with higher 120 min survival rate ( 20% vs. 90%,∗2=9.899, P=0.005; 30% vj. 90%,∗2=7.5, P=0.02) . CO was higher in MG than that in other groups at all given intervals in the early stage of post-resuscitation(P<0.05). MAP levels were significantly higher in MG and HG compared with CG and LG at given intervals 15 min after ROSC (P相似文献   

Effect of mild hypothermia on the oxidative stress induced myocardlal injury after cardiopulmonary resuscitation北大核心CSCD

Objective To observe the effects of mild hypothermia on the myocardial mitochondrial injmy induced by oxidative stress after restoration of spontaneous circulation (ROSC) in rat of cardiac arrest model. Methods Eighteen male Wistar rats were randomly (raudom number) divided into normal temperature group and mild hypothermia group after ROSC. Ultrasound was used to measure the left ventricular ejection fraction (EF), shortening fraction (FS) and stroke volume (SV). The levels of glutethione (GSH), malondialdehyde (MDA) and adenosine triphosphate (ATP) in myocardium were detected. The ultramicroscopic structure of myocardial mitochondria was observed under transmission electron microscope at 4 h after ROSC. Results There were no significant differences in basic life support (BIS) time, dosage of epinephrine and number of defibrillation attempt between two groups (P > 0.05). The concentrations of GSH and ATP in myocardium of rats in hypothermia group were significantly higher than those in normal temperature group, while the level of MDA was significantly lower in hypothermia group than that in normal temperature group. Echocardiographic findings showed that hypothermia could significantly improve the EF, FS and SV after ROSC. The hypothermia decreased the myocardial mitochondria injury rather than normothermia [mitochondrial injury score: (0. 21 ±0.04) vs. ( 0.42 ±0. 08), P <0. 05]. Conclusions In this model, mild hypothermia can decrease myocardial oxidative stress injury, improving the cardiac function after ROSC.     

心肌缺血/再灌注损伤后瘦素的改变及机制初探

Objective To explore the effect of rat myocardial ischemia/reperfusion (I/R) injury on serum Leptin, endothelin (ET), C-reactive protein (CRP) and myocardial Leptin expression, and discuss the role of Leptin in myocardial I/R injury.Methods Fifty Sprague-Dawley (SD) rats were randomly divided into sham-operation, ischemia and I/R 1, 2, 3 hours groups, with 10 rats in each group.Anterior descending artery of the left coronary artery was ligated for 45 minutes and released for 1, 2 and 3 hours to establish myocardial I/R model, and the said artery of the rats in sham-operation group was not ligated.Blood from left femoral artery was collected at different time points, and serum Leptin, ET and CRP contents were detected.Myocardial tissue was harvested, and stained with hematoxylin-eosin (HE)and immunohistochemistry for its observation of the myocardial pathological changes and Leptin protein expression.Results Serum Leptin content (μg/L) of ischemia group was significantly lower than that of sham-operation group (4.69 ± 1.67 vs.6.48 ± 2.02, P＜ 0.05); as the reperfusion time was prolonged,serum Leptin level increased gradually, and the level of I/R 3-hour group recovered to that before injury [(6.59±2.58) μg/L].ET content (ng/L) of ischemia group was significantly higher than that of sham-operation group (110.58 ± 37.86 vs.80.74 ± 34.43, P＜0.05), the levels of ET in I/R 1, 2 and 3 hours groups were significantly lower than those of ischemia group (35.87 ± 13.56, 31.98 ±10.88,34.56±14.37 vs.110.58±37.86, all P＜0.05).CRP content (mg/L) of ischemia group was significantly higher than that of sham-operation group (13.12±4.82 vs.3.24±1.72,P＜0.01); as the reperfusion time was prolonged, serum CRP level increased gradually,and the levels of I/R 1, 2 and 3 hours groups were significantly higher than those of ischemia group (18.37 ± 6.48, 24.30 ± 9.51, 27.08 ± 8.32 vs.13.12 ±4.82, all P＜0.05).Pathological examination showed that there was necrosis of ischemic myocardial cells in ischemia group, with mild congestion and edema in interstitial spaces.After I/R injury, the myocardial cells showed coagulative necrosis, and there was severe congestion of myocardial interstitia.Immunohistochemistry results showed that there was a tendency of decrease in Leptin protein expression in the early phase but increase in the late phase after the injury.Conclusion Leptin content in the serum and myocardial tissue decreases significantly in the early phase after myocardial I/R but increases gradually in the rehabilitative phase, suggesting that Leptin maybe a stress protective factor against I/R-induced myocardial injury.There is a possible association between Leptin and the early increase followed by a delayed decrease of ET as well as the increase of CRP.     

The mobilization of stem cells promote the recovery of the ischemia brain injury after cardiopulmonary resuscitation北大核心CSCD

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.     

Protective effects of TAK-242 against coronary microembolization in rat associated with involvement of TLR4/NF-κB signaling pathway北大核心CSCD

Objective To investigate the role of TI.R4/NK-kB signaling pathway under the action of TAK-242 in the cardiomyocyte apoptosis after coronary micro-embolism (CME) in rats. Methods Forty- five rats were randomized (random number) into three groups: sham operation, CME and CME plus TAK- 242 groups (n = 15 per group). CME was induced by injecting polyethylene microspheres (42 p.m) into the left ventricle except the sham group. CME plus TAK-242 group was treated with TAK-242 (2 mg/kg) via the tail vein of mice 30 min before CME modeling. Cardiac function was evaluated 6 h after operation. Tissue biopsy was stained with HBFP to measure the size of infarction area. TUNEK assay was used to detect cardiomyocyte apoptosis. Western blot and qPCR were used to evaluate the protein levels and mKNA expressions of TLR4, NF-kB p65 and cleaved caspase-3, resjjectively. Statistical analysis was performed using one-way analysis of variance followed by LSD-/ test. Results Compared with the sham group, left ventricular ejection fraction (LVEF) in the CME group was significantly decreased [ (68.91 ± 4. 12) % vs. (84. 80 ± 2. 51 ) % , P<0. 05], and the infarction area (P<0. 05) , the apoptosis index [(3. 36 ± 0.63) % vs. (0.19 ± 0.08) %, P < 0.05 ], the mRN A expressions of TLR4, NF-kB p65 and cleaved caspase-3 in CME group were increased significantly (all P <0. 05). Compared with CME group, LVEF in the CME plus TAK-242 group was significantly improved [ (75. 58 ± 5. 01) % vs. (68. 91 ± 4. 12) % , P> < 0. 05 ], and the infarction area [ (8.58 ± 2. 12) % vs. (14.65 ± 4.23) % , P< 0.05], the apoptosis index [ (1. 43 ± 0. 51) % vs. (3. 36 ± 0. 63) % , P <0. 05], the mRN A expressions of TLR4, NF-kB p65 and cleaved caspase-3 in CME + TAK-242 group were decreased significantly (all P <0. 05). Conclusions TAK-242 effectively improved CME-induced cardiac dysfunction by regulating TLR4/NF-kB signaling pathway and then reducing the cardiomyocyte apoptosis.     

Effect of ulinastatin on expressions of serum cardiac troponin Ⅰ, myocardial tumor necrosis factor-α and endothelin-1 in septic rats

Objective To investigate the myocardial protective effects of different dosage of ulinastatin (UTI) and the possible mechanism in septic rats.Methods Forty male Sprague-Dawley (SD) rats were randomly divided into five groups: control group, sham group, model group, UTI in low dose or high dose group.Cecal ligation and puncture (CLP) was adopted to reproduce animal model of sepsis.Left ventricular myocardium was harvested and blood samples were collected at 24 hours after successful establishment of animal model.Serum cardiac troponin Ⅰ (cTnI), the contents of myocardial tumor necrosis factor-α (TNF-α)and endothelin-1 (ET-1) were measured, and myocardial pathological changes were observed.Results In the model group, the level of serum cTnI, and the expressions of myocardial TNF-α and ET-1 were much higher than those in control group [cTnI (μg/L): 7.58 ± 0.53 vs.1.05 ± 0.21, TNF-α (pg/g): 945.6 ±72.0 vs.238.2±35.2, ET-1 (pg/g): 776.8±123.9 vs.170.1±28.3, all P＜0.01].There were no differences in the levels of serum cTnI, myocardial TNF-α and ET-1 between low dose UTI group and the model group [cTnI (μg/L): 7.21± 0.51 vs.7.58 ± 0.53, TNF-α(pg/g):910.5 ± 96.6 vs.945.6 ± 72.0,ET-1 (pg/g): 714.0±66.7 vs.776.8±123.9, all P＞0.05].However, serum cTnI, myocardial TNF-α and ET-1 were lower significantly in high dose UTI group than in model group [cTnI (μg/L): 4.30±0.84 vs.7.58±0.53, TNF-α(pg/g): 430.5±75.6 vs.945.6±72.0, ET-1 (pg/g): 377.1±39.0 vs.776.8±123.9, all P＜0.01].Conclusion High dose (but not low dose) UTI may protect myocardium from the damage resulted from sepsis in a rat model, probably by lowering expressions of TNF-α and ET-1.     

限制性液体复苏对肝脏缺血-再灌注损伤的影响

Objective To investigate the effects of limited resuscitation on hepatic ischernia-reperfusion in-jury in rots with hemorrhagic shock. Method Uncontrolled hemorrhagic shock was induced in 54 rats by transect-ing the middle branch of the splenic artery to produce standardized massive splenic injury. Resuscitation started when the mean arterial pressure (MAP) reached 40 mmHg. The rats were randomly divided (n = 9per group) in-to sham-operated group (SS), or one of five treatment groups in which infusion of Ringer' s solution was continually administrated to maintain MAP at 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) or 100 mmHg (RS100) for 45 minutes (T45 point). After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to increase the MAP to 100 mmHg for 120 minutes (T165 point), which was followed by obser-vation for 240 minutes (T405 point). All animals were observed for 240 minutes or until death. Blood specimens were collected at TO, T45, T165 and T405 for determination of blood lactate levels. At the end of the experiment,a small amount of hepatic tissue was collected to measure tissue blood perfusion, total antioxidative capacity (TAOC), Na+K+ ATPase activity and malondialdehyde (MDA) levels. Results At T405, the blood lactate lev-els in the RS80 and RS100 groups [(3.60±0.68) and (3.84 ± 1.09) mmol/L, respectively] were significantly higher than those in the SS, RS40, RS50 and RS60 groups [(2.00±0.66),(2.74±1.45),(2.43 +0.94) and (2.07±0.95) mmol/L, respectively;all:P < 0.05]. The MDA levels were significantly higher in the RS80 and RS100[(7.32±0.31) and (7.71±0.23) nmol/mg,respectively] than those in the SS, RS40, RS50 and RS60 groups[(4.95±0.80),(6.14±0.94),(6.42±0.48) and (6.84±0.36) nmol/mg, respeetively;all: P <0.05]. The Na+ K+ ATPase and TAOC levels were significantly lower in all of the RS groups than those in the SS group (all: P < 0.05), and those in the RS80 and RS100 groups was significantly lower than those in the RS40,RS50 and RS60 groups (all: P <0.05). Blood perfusion in the RS80 and RS100 groups was significantly lower than that in the other groups (all: P < 0.05). Conclusions If hemorrhage is uncontrolled, limited resuscitation appears to balance the needs for organ perfusion, improve the microcircttlation and decrease lactate levels. Fur-thermore, limited resuscitation could decrease ischemia-reperfusion injury in liver tissue.     

限制性液体复苏对肝脏缺血-再灌注损伤的影响

Objective To investigate the effects of limited resuscitation on hepatic ischernia-reperfusion in-jury in rots with hemorrhagic shock. Method Uncontrolled hemorrhagic shock was induced in 54 rats by transect-ing the middle branch of the splenic artery to produce standardized massive splenic injury. Resuscitation started when the mean arterial pressure (MAP) reached 40 mmHg. The rats were randomly divided (n = 9per group) in-to sham-operated group (SS), or one of five treatment groups in which infusion of Ringer' s solution was continually administrated to maintain MAP at 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) or 100 mmHg (RS100) for 45 minutes (T45 point). After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to increase the MAP to 100 mmHg for 120 minutes (T165 point), which was followed by obser-vation for 240 minutes (T405 point). All animals were observed for 240 minutes or until death. Blood specimens were collected at TO, T45, T165 and T405 for determination of blood lactate levels. At the end of the experiment,a small amount of hepatic tissue was collected to measure tissue blood perfusion, total antioxidative capacity (TAOC), Na+K+ ATPase activity and malondialdehyde (MDA) levels. Results At T405, the blood lactate lev-els in the RS80 and RS100 groups [(3.60±0.68) and (3.84 ± 1.09) mmol/L, respectively] were significantly higher than those in the SS, RS40, RS50 and RS60 groups [(2.00±0.66),(2.74±1.45),(2.43 +0.94) and (2.07±0.95) mmol/L, respectively;all:P < 0.05]. The MDA levels were significantly higher in the RS80 and RS100[(7.32±0.31) and (7.71±0.23) nmol/mg,respectively] than those in the SS, RS40, RS50 and RS60 groups[(4.95±0.80),(6.14±0.94),(6.42±0.48) and (6.84±0.36) nmol/mg, respeetively;all: P <0.05]. The Na+ K+ ATPase and TAOC levels were significantly lower in all of the RS groups than those in the SS group (all: P < 0.05), and those in the RS80 and RS100 groups was significantly lower than those in the RS40,RS50 and RS60 groups (all: P <0.05). Blood perfusion in the RS80 and RS100 groups was significantly lower than that in the other groups (all: P < 0.05). Conclusions If hemorrhage is uncontrolled, limited resuscitation appears to balance the needs for organ perfusion, improve the microcircttlation and decrease lactate levels. Fur-thermore, limited resuscitation could decrease ischemia-reperfusion injury in liver tissue.     

Effect of ulinastatin on expressions of serum cardiac troponin Ⅰ, myocardial tumor necrosis factor-α and endothelin-1 in septic rats

Objective To investigate the myocardial protective effects of different dosage of ulinastatin (UTI) and the possible mechanism in septic rats.Methods Forty male Sprague-Dawley (SD) rats were randomly divided into five groups: control group, sham group, model group, UTI in low dose or high dose group.Cecal ligation and puncture (CLP) was adopted to reproduce animal model of sepsis.Left ventricular myocardium was harvested and blood samples were collected at 24 hours after successful establishment of animal model.Serum cardiac troponin Ⅰ (cTnI), the contents of myocardial tumor necrosis factor-α (TNF-α)and endothelin-1 (ET-1) were measured, and myocardial pathological changes were observed.Results In the model group, the level of serum cTnI, and the expressions of myocardial TNF-α and ET-1 were much higher than those in control group [cTnI (μg/L): 7.58 ± 0.53 vs.1.05 ± 0.21, TNF-α (pg/g): 945.6 ±72.0 vs.238.2±35.2, ET-1 (pg/g): 776.8±123.9 vs.170.1±28.3, all P＜0.01].There were no differences in the levels of serum cTnI, myocardial TNF-α and ET-1 between low dose UTI group and the model group [cTnI (μg/L): 7.21± 0.51 vs.7.58 ± 0.53, TNF-α(pg/g):910.5 ± 96.6 vs.945.6 ± 72.0,ET-1 (pg/g): 714.0±66.7 vs.776.8±123.9, all P＞0.05].However, serum cTnI, myocardial TNF-α and ET-1 were lower significantly in high dose UTI group than in model group [cTnI (μg/L): 4.30±0.84 vs.7.58±0.53, TNF-α(pg/g): 430.5±75.6 vs.945.6±72.0, ET-1 (pg/g): 377.1±39.0 vs.776.8±123.9, all P＜0.01].Conclusion High dose (but not low dose) UTI may protect myocardium from the damage resulted from sepsis in a rat model, probably by lowering expressions of TNF-α and ET-1.     

限制性液体复苏对肝脏缺血-再灌注损伤的影响

Objective To investigate the effects of limited resuscitation on hepatic ischernia-reperfusion in-jury in rots with hemorrhagic shock. Method Uncontrolled hemorrhagic shock was induced in 54 rats by transect-ing the middle branch of the splenic artery to produce standardized massive splenic injury. Resuscitation started when the mean arterial pressure (MAP) reached 40 mmHg. The rats were randomly divided (n = 9per group) in-to sham-operated group (SS), or one of five treatment groups in which infusion of Ringer' s solution was continually administrated to maintain MAP at 40 (RS40), 50 (RS50), 60 (RS60), 80 (RS80) or 100 mmHg (RS100) for 45 minutes (T45 point). After the bleeding was controlled, resuscitation was continued with Ringer's solution and whole blood (2:1) to increase the MAP to 100 mmHg for 120 minutes (T165 point), which was followed by obser-vation for 240 minutes (T405 point). All animals were observed for 240 minutes or until death. Blood specimens were collected at TO, T45, T165 and T405 for determination of blood lactate levels. At the end of the experiment,a small amount of hepatic tissue was collected to measure tissue blood perfusion, total antioxidative capacity (TAOC), Na+K+ ATPase activity and malondialdehyde (MDA) levels. Results At T405, the blood lactate lev-els in the RS80 and RS100 groups [(3.60±0.68) and (3.84 ± 1.09) mmol/L, respectively] were significantly higher than those in the SS, RS40, RS50 and RS60 groups [(2.00±0.66),(2.74±1.45),(2.43 +0.94) and (2.07±0.95) mmol/L, respectively;all:P < 0.05]. The MDA levels were significantly higher in the RS80 and RS100[(7.32±0.31) and (7.71±0.23) nmol/mg,respectively] than those in the SS, RS40, RS50 and RS60 groups[(4.95±0.80),(6.14±0.94),(6.42±0.48) and (6.84±0.36) nmol/mg, respeetively;all: P <0.05]. The Na+ K+ ATPase and TAOC levels were significantly lower in all of the RS groups than those in the SS group (all: P < 0.05), and those in the RS80 and RS100 groups was significantly lower than those in the RS40,RS50 and RS60 groups (all: P <0.05). Blood perfusion in the RS80 and RS100 groups was significantly lower than that in the other groups (all: P < 0.05). Conclusions If hemorrhage is uncontrolled, limited resuscitation appears to balance the needs for organ perfusion, improve the microcircttlation and decrease lactate levels. Fur-thermore, limited resuscitation could decrease ischemia-reperfusion injury in liver tissue.