Objective:To investigate the protective function of tocilizumab in human cardiac myocytes ischemia-reperfusion injury.Methods:The human cardiac myocytes were treated by tocilizumab with different concentrations(1.0 mg...Objective:To investigate the protective function of tocilizumab in human cardiac myocytes ischemia-reperfusion injury.Methods:The human cardiac myocytes were treated by tocilizumab with different concentrations(1.0 mg/mL,3.0 mg/mL,5.0 mg/mL) for 24 h.then cells were cultured in ischemia environment for 24 h and reperfusion environment for 1 h.The MTT and flow cytometry were used to detect the proliferation and apoptosis of human cardiac myocytes,respectively.The mRNA and protein expressions of Bcl-2 and Bax were measured by qRT-PCR and western blot,respectively.Results:Compared to the negative group,pretreated by tocilizumab could significantly enhance the proliferation viability and suppress apoptosis of human cardiac myocytes after suffering ischemia reperfusion injury(P<0.05).The expression of Bcl-2 in tocilizumab treated group were higher than NC group(P<0.05).while the Bax expression were lower(P<0.05).Conclusions:Tocilizumab could significantly inhibit apoptosis and keep the proliferation viability of human cardiac myocytes after suffering ischemia reperfusion injury.Tocilizumab may obtain a widely application in the protection of ischemia reperfusion injury.展开更多
BACKGROUND: Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia- reperfusion injury. Endoplasmic reticulum (ER) stress is involved in ischemia-reperfusion injury, but its ...BACKGROUND: Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia- reperfusion injury. Endoplasmic reticulum (ER) stress is involved in ischemia-reperfusion injury, but its role in donation after cardiac death (DCD) liver transplantation is not clear and the effect of ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenyl butyric acid (PBA), on the prognosis of recipient of DCD liver transplantation remains unclear. METHODS: Male Sprague-Dawley rats (8-10 weeks) were randomly divided into control group: liver grafts without warm ischemia were implanted; DCD group: warm ischemia time of the liver grafts was 60 minutes; TUDCA and PBA groups: based on the DCD group, donors were intraperitoneally injected with TUDCA or PBA 30 minutes before the organ procurements. Serum aminotransferase levels, oxidative stress activation and expression of ER stress signal molecules were evaluated. Pathological examinations were performed. The survivals of the recipients in each group were compared for 14 days.RESULTS: Compared with the control group, DCD rats had significantly higher levels of serum aminotransferase at 6 hours, 1 day and 3 days after operation (P〈0.01, 0.01 and 0.05, respectively) and oxidative indices (P〈0.01 for both malondialdehyde and 8-hydroxy deoxyguanosine), more severe liver damage (P〈0.01) and up-regulated ER stress signal expressions (P〈0.01 for GRP78, phos-eIF2al, CHOP, ATF-4, ATF-6, PERK, XBP-1 and pro-caspase-12). All recipients died within 3 days after liver transplantation. Administration of TUDCA or PBA significantly decreased aminotransferase levels (P〈0.05), increased superoxide dismutase activities (P〈0.01), alleviated liver damage (P〈0.01), down-regulated ER stress signal expressions (P〈0.01) and improved postoperative survivals (P〈0.01). CONCLUSIONS: ER stress was involved with DCD liver trans- plantation in rats. Preoperative intraperitoneally injection of TUDCA or PBA protected ER stress and improved prognosis.展开更多
Cerebral ischemia/reperfusion injury is partially mediated by thrombin, which causes brain damage through protease-activated receptor 1(PAR1). However, the role and mechanisms underlying the effects of PAR1 activati...Cerebral ischemia/reperfusion injury is partially mediated by thrombin, which causes brain damage through protease-activated receptor 1(PAR1). However, the role and mechanisms underlying the effects of PAR1 activation require further elucidation. Therefore, the present study investigated the effects of the PAR1 antagonist SCH79797 in a rabbit model of global cerebral ischemia induced by cardiac arrest. SCH79797 was intravenously administered 10 minutes after the model was established. Forty-eight hours later, compared with those administered saline, rabbits receiving SCH79797 showed markedly decreased neuronal damage as assessed by serum neuron specific enolase levels and less neurological dysfunction as determined using cerebral performance category scores. Additionally, in the hippocampus, cell apoptosis, polymorphonuclear cell infiltration, and c-Jun levels were decreased, whereas extracellular signal-regulated kinase phosphorylation levels were increased. All of these changes were inhibited by the intravenous administration of the phosphoinositide 3-kinase/Akt pathway inhibitor LY29004(3 mg/kg) 10 minutes before the SCH79797 intervention. These findings suggest that SCH79797 mitigates brain injury via anti-inflammatory and anti-apoptotic effects, possibly by modulating the extracellular signal-regulated kinase, c-Jun N-terminal kinase/c-Jun and phosphoinositide 3-kinase/Akt pathways.展开更多
Initial ischemia/reperfusion injury (IRI) may have an impact on recipient immune responses after transplantation. Allograft inflammatory factor-1 (AIF-1) has been implicated in the regulation of inflammation associate...Initial ischemia/reperfusion injury (IRI) may have an impact on recipient immune responses after transplantation. Allograft inflammatory factor-1 (AIF-1) has been implicated in the regulation of inflammation associated with organ rejection. We hypothesized that it is either passively released from injured tissues during organ procurement, or actively secreted by allograft infiltrating cells contributing to allograft dysfunction. We investigated the impact of IRI in an in vitro study of human heart tissue during the process of transplantation. The mRNA expression levels for both isoforms of the AIF-1, I2 and I3 were significantly increased after 30 minutes reperfusion (AIF-1 I2: p 0.01 vs. AIF-1 I3: p 0.005). Expression levels for IL-18 and the TLRs were increased after 30 minutes of reperfusion. Only IL-18 and TLR-2 were statistically significant (IL-18: p 0.0001 vs. TLR-2: p 0.01). The mRNA expression levels for AIF-1 I2 and IL-18 were decreased from the original levels of ischemia after 60 and 90 minutes reperfusion. The TLR-2 and -4 were presented with minimal levels of reduction after 60 minutes. However, mRNA expression levels for all were decreased to the original levels of ischemia after 90 minutes, except for AIF-1 I3, but the difference was not statistically significant. AIF-1 and IL-18 were specifically detected in myocytes and interstitial tissues by immunohistochemistry (IHC) stain after IRI. TLR-4 was non-specific, and TLR2 was minimally expressed. The study discusses the evidence supporting that the AIF-1 may have therapeutic potential for strategies in the control of innate immune responses early on, after transplantation.展开更多
Background: Reduction of myocardial reperfusion injury during cardiopulmonary bypass is an essential requirement for increasing the success rate, decreasing morbidity and mortality of open-heart surgery. Aim: To study...Background: Reduction of myocardial reperfusion injury during cardiopulmonary bypass is an essential requirement for increasing the success rate, decreasing morbidity and mortality of open-heart surgery. Aim: To study the role of pre-operative oral nicorandil in decreasing reperfusion cardiac injury in patients subjected to cardiac valve surgery. Patients and Methods: The study included 62 patients, who were equally randomized into two groups: nicorandil group and control group. Pre-operative, intra-operative and post- operative data were reported and analyzed. Left Ventricle Ejection Fraction (LVEF) was estimated pre-operatively and postoperatively for both groups. Troponin I, creatine kinase-muscle/brain (CK-MB), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured before surgery by 24 hours then 4, 12 and 48 hours after aortic cross clamp removal. Results: Nicorandil considerably decreased TNF-α and IL-6 after 4 and 12 hours following the removal of aortic clamping. It also reduced troponin-I and CKMB at the same time points. However, there were no important changes in IL-6, TNF-α, troponin-I and CK-MB levels in control group in comparison to nicorandil group in the next 48 hours following the removal of aortic clamping. Conclusions: Pre-operative oral nicorandil expressively decreased myocardial reperfusion damage during open heart valve operations, this evidenced by the decrease in the postoperative use of inotropic drugs, considerable reduction of postoperative elevation of cardiac enzymes and inflammatory cytokines with no reported complications.展开更多
Hearts of pressure-overload hypertrophy show an increased activation of intracardiac renin-angiotensin system which may contribute to ischemia and reperfusion injury. The purpose of this study is to evaluate whether t...Hearts of pressure-overload hypertrophy show an increased activation of intracardiac renin-angiotensin system which may contribute to ischemia and reperfusion injury. The purpose of this study is to evaluate whether the hypertrophied myocardium is more vulnerable to ischemia and reperfusion injury and to find out its relation to the cardiac renin-angiotensin system. Hypertrophied rat hearts induced by abdominal aortic banding for 6 weeks were subjected to 2 hours of hypothermic ischemic arrest followed by 30 minutes of reperfusion, and their cardiac function recovery was compared with that of sham-operated normal control hearts. The cardiac renin activity and angiotensin II content before ischemia and after reperfusion were determined. It was found that both the pre-ischemic renin activity and angiotensin II level were higher in hypertrophied myocardium than those in the control: ischemia and reperfusion injury increased both renin activity and angiotensin II content in the two groups, but the renin activity and angiotensin II level were further elevated after reperfusion in the hypertrophied hearts than those in the control hearts. Meanwhile, the cardiac function recovery after 30 minutes reperfusion in the hypertrophied hearts was poorer than that in the control. Correlation analysis revealed that there was a negative correlation between the cardiac output recovery and the myocardial angiotensin II content (r=-0.841), P<0.001), It is concluded that ischemia and reperfusion injury can activate cardiac renin-angiotensin system in isolated rat heart, which may be responsible for the increased susceptibility of the hypertrophied myocardium to ischemia and reperfusion injury.展开更多
OBJECTIVE: To determine the cardioprotective ef- fect of magnesium lithospermate B (MLB) on myo- cardial ischemia/reperfusion (MI/R) injury and to in- vestigate the antioxidant potential in vivo and in vitro. MET...OBJECTIVE: To determine the cardioprotective ef- fect of magnesium lithospermate B (MLB) on myo- cardial ischemia/reperfusion (MI/R) injury and to in- vestigate the antioxidant potential in vivo and in vitro. METHODS: MI/R injury was induced by the occlu- sion of left anterior descending coronary artery for 30 min followed by reperfusion for 3 h in rats. After reperfusion, hearts were harvested to assess infarct size, histopathological damages, the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and malondialdehyde (MDA). Blood samples were collected to determine serum levels of creatine kinase-MB (CK-MB), cardiac troponin (cTnl) and lactate dehydrogenase (LDH). Furthermore, simulatedischemia/reperfusion (SI/R) injury in vitro was established by oxygen and glucose deprivation (OGD) for 2 h followed by 24-hour recovery period in cardiomyocytes. The activity of LDH in the cultured su- pernatant and the levels of intracellular reactive oxygen species (ROS), SOD and MDA in cardiomyo- cytes were also measured. Finally, cardiomyocytes apoptosis was determined with flow cytometry. RESULTS: MLB significantly limited infarct size, ameliorated histopathological damages and prevented leakage of CK-MB, cTnl and LDH. Additional- ly, SOD, CAT, GPx and GSH activities were notably increased by MLB, along with the MDA content decreased as compared with the model group in rats. In vitro study, MLB also decreased LDH activity in the cultured supernatant, increased SOD activity in cardiomyocytes, reduced intracellular ROS and MDA levels, and significantly suppressed cardiomyocytes apoptosis. CONCLUSION: MLB possessed remarkably cardioprotective effects on MI/R injury in vivo and in vitro. The protection of MLB may contribute to its antioxidant properties.展开更多
BACKGROUND: Resuscitation after cardiac arrest (CA) with a whole-body ischemia–reperfusion injury causes brain injury and multiple organ dysfunction (MODS). This study aimed to determine whether mild systemic hy...BACKGROUND: Resuscitation after cardiac arrest (CA) with a whole-body ischemia–reperfusion injury causes brain injury and multiple organ dysfunction (MODS). This study aimed to determine whether mild systemic hypothermia could decrease multiple organ dysfunctions after resuscitation from cardiac arrest.METHODS: The patients who had been resuscitated after cardiac arrest were reviewed. During the resuscitation they had been assigned to undergo therapeutic hypothermia (target temperature, 32°C to 34°C, measured in the rectum) over a period of 24 to 36 hours or to receive standard treatment with normothermia. Markers of different organ injury were evaluated for the ? rst 72 hours after recovery of spontaneous circulation (ROSC).RESULTS: At 72 hours after ROSC, 23 patients in the hypothermia group for whom data were available had favorable neurologic, myocardial, hepatic and pulmonic outcomes as compared with 26 patients in the normothermia group. The values of renal function were not signi? cantly different between the two groups. However, blood coagulation function was badly injured in the hypothermia group.CONCLUSION: In the patients who have been successfully resuscitated after cardiac arrest, therapeutic mild hypothermia can alleviate dysfunction after resuscitation from cardiac arrest.展开更多
Acute interruption of arterial blood flow to the extremities is often associated with significant morbidity and mortality. Broad spectrum mitogenic and non mitogenic activities of FGFs inspired us to study its protect...Acute interruption of arterial blood flow to the extremities is often associated with significant morbidity and mortality. Broad spectrum mitogenic and non mitogenic activities of FGFs inspired us to study its protecting effects on tissue injuries in ischemia reperfusion condition. We found that systemic administration of aFGF after reperfusion onset prevented severe skeletal muscle injuries. In rats treated with aKGF, the tissue edema was reduced significantly, the tissue viability was increased, and the muscle fibers contained more succinate dehydrogenase (SDH) and adenosine triphosphatasc (ATPase). The pathological results supported the concept of improved prevention with aFGF treatment. The possible tissue protection by aFGF may come from its ability to regulate the concentration of evtra- and intracellular calcium ion. Besides, it may moderate other Ca2+ dependent enzyme conversion processes. Also, it may take part in the vascular tone regulation under ischemia and reperfusion conditions. These results suggest further study of tissue ischemia prevention with FGF and its possible mechanisms in the future.展开更多
Myocardial ischemia and reperfusion(I/R) is a common problem in clinic and there is no satisfactory method for prevention or treatment of I/R injury so far.Chronic intermittent hypobaric hypoxia(CIHH),similar to the c...Myocardial ischemia and reperfusion(I/R) is a common problem in clinic and there is no satisfactory method for prevention or treatment of I/R injury so far.Chronic intermittent hypobaric hypoxia(CIHH),similar to the concept of ischemia preconditioning(IPC)or altitude hypoxia adaptation(AHA),has been recognized to confer a protective effect on heart against I/R injury with a longer protective effect than IPC and a less adverse effect than AHA.It has been proved that CIHH increases myocardial tolerance to ischemia or hypoxia,reserving cardiac function and preventing arrhythmia during I/R.Multiple mechanisms or pathway underlying the cardiac protection of CIHH have been proposed,such as induction of heatshock protein,enhancement of myocardial antioxidation capacity,increase of coronary flow and myocardial capillary angiogenesis,activation of adenosine triphosphate(ATP)-sensitive potassium channels,inhibition of mitochondrial permeability transition pores,and activation of protein kinase C(PKC) and induced nitric oxide synthase(iNOS).In addition,CIHH has been found having many beneficial effects on the body,such as promotion of health,increase of oxygen utilization,and prevention or treatment for some diseases.The beneficial effects of CIHH and potential mechanisms are reviewed mainly based on the researches performed by our group.展开更多
Purpose: Prevention of myocardial injury is essential during cardiac surgery. Both crystalloid and blood cardioplegia are popular methods for myocardial protection. Most experimental studies have been in favor of bloo...Purpose: Prevention of myocardial injury is essential during cardiac surgery. Both crystalloid and blood cardioplegia are popular methods for myocardial protection. Most experimental studies have been in favor of blood cardioplegia. The objective of this study is to determine whether the use of warm blood cardioplegia (BCP) is superior to crystalloid cardioplegia (CCP) by means of myocardial injury markers and clinical outcome parameters. Materials and Methods: In a consecutive series of 293 patients, the first 150 received crystalloid cardioplegia, whereas the next 143 patients received blood cardioplegia. Postoperative myocardial injury was assessed by CTnI and CK-MB. Perioperative morbidity and mortality and clinical outcome parameters (need for inotropic support, ICU and hospital stay) were recorded. An unpaired student t-test was performed to analyse continuous postoperative variables relating to myocardial damage. The presence of possible confounders influencing the CTnI or CK-MB concentrations was tested using a student t-test for continuous variables, for categorical variables ANOVA was used. A final longitudinal model was created for CTnI and CK-MB. CTnI was analyzed by a mixed model with random intercept and slope. For all tests performed, statistical significance was 5%. Results: Both groups were well matched with respect to preoperative variables. No significant difference could be found in maximum postoperative levels of CTnI (8.8 ± 18.4 μg/l in BCP vs 9.6 ± 16.5 μg/l in CCP, p = 0.6455) or CK-MB (19.2 ± 31.0 μg/l in BCP vs 26.4 ± 41.5 μg/l in CCP, p = 0.1209). Nor was there any significant difference in other postoperative variables. Testing treatment effect over time proved only significant influence of the surgical intervention type on CTnI levels in time (p < 0.001). Conclusion: This study could not show significantly higher myocardial injury in the group of patients receiving crystalloid cardioplegia versus warm blood cardioplegia. This suggests that warm blood cardioplegia does not confer superior myocardial protection. Surgical intervention type has an important effect on CTnI concentration in time, while the type of cardioplegia does not.展开更多
Experimental, clinical and epidemiologic studies have provided strong evidence that physical training has beneficial effects on cardiovascular health. Numerous investigations have demonstrated that exercise increases ...Experimental, clinical and epidemiologic studies have provided strong evidence that physical training has beneficial effects on cardiovascular health. Numerous investigations have demonstrated that exercise increases coronary blood flow and myocardial perfusion. Importantly, training also can stimulate angiogenesis and accelerate collateral vessel growth in animal models with coronary artery occlusion. Cardiac adaptation such as increased vascularity or capillary density has been evidenced after regular endurance exercises. More recently, several studies indicate that physical training induces high levels of myocardial heat shock protein and antioxidant protein expression, which may play an important role in myocardial protection against ischemia-reperfusion injury.展开更多
基金supported by a grant from the Health Department Foundation of Zhejiang Province(2010KYA102)
文摘Objective:To investigate the protective function of tocilizumab in human cardiac myocytes ischemia-reperfusion injury.Methods:The human cardiac myocytes were treated by tocilizumab with different concentrations(1.0 mg/mL,3.0 mg/mL,5.0 mg/mL) for 24 h.then cells were cultured in ischemia environment for 24 h and reperfusion environment for 1 h.The MTT and flow cytometry were used to detect the proliferation and apoptosis of human cardiac myocytes,respectively.The mRNA and protein expressions of Bcl-2 and Bax were measured by qRT-PCR and western blot,respectively.Results:Compared to the negative group,pretreated by tocilizumab could significantly enhance the proliferation viability and suppress apoptosis of human cardiac myocytes after suffering ischemia reperfusion injury(P<0.05).The expression of Bcl-2 in tocilizumab treated group were higher than NC group(P<0.05).while the Bax expression were lower(P<0.05).Conclusions:Tocilizumab could significantly inhibit apoptosis and keep the proliferation viability of human cardiac myocytes after suffering ischemia reperfusion injury.Tocilizumab may obtain a widely application in the protection of ischemia reperfusion injury.
基金supported by a grant from the National Natural Science Foundation of China (81273262)
文摘BACKGROUND: Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia- reperfusion injury. Endoplasmic reticulum (ER) stress is involved in ischemia-reperfusion injury, but its role in donation after cardiac death (DCD) liver transplantation is not clear and the effect of ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenyl butyric acid (PBA), on the prognosis of recipient of DCD liver transplantation remains unclear. METHODS: Male Sprague-Dawley rats (8-10 weeks) were randomly divided into control group: liver grafts without warm ischemia were implanted; DCD group: warm ischemia time of the liver grafts was 60 minutes; TUDCA and PBA groups: based on the DCD group, donors were intraperitoneally injected with TUDCA or PBA 30 minutes before the organ procurements. Serum aminotransferase levels, oxidative stress activation and expression of ER stress signal molecules were evaluated. Pathological examinations were performed. The survivals of the recipients in each group were compared for 14 days.RESULTS: Compared with the control group, DCD rats had significantly higher levels of serum aminotransferase at 6 hours, 1 day and 3 days after operation (P〈0.01, 0.01 and 0.05, respectively) and oxidative indices (P〈0.01 for both malondialdehyde and 8-hydroxy deoxyguanosine), more severe liver damage (P〈0.01) and up-regulated ER stress signal expressions (P〈0.01 for GRP78, phos-eIF2al, CHOP, ATF-4, ATF-6, PERK, XBP-1 and pro-caspase-12). All recipients died within 3 days after liver transplantation. Administration of TUDCA or PBA significantly decreased aminotransferase levels (P〈0.05), increased superoxide dismutase activities (P〈0.01), alleviated liver damage (P〈0.01), down-regulated ER stress signal expressions (P〈0.01) and improved postoperative survivals (P〈0.01). CONCLUSIONS: ER stress was involved with DCD liver trans- plantation in rats. Preoperative intraperitoneally injection of TUDCA or PBA protected ER stress and improved prognosis.
基金supported by the Natural Science Foundation of Hubei Province of China,No.2010CDB09101
文摘Cerebral ischemia/reperfusion injury is partially mediated by thrombin, which causes brain damage through protease-activated receptor 1(PAR1). However, the role and mechanisms underlying the effects of PAR1 activation require further elucidation. Therefore, the present study investigated the effects of the PAR1 antagonist SCH79797 in a rabbit model of global cerebral ischemia induced by cardiac arrest. SCH79797 was intravenously administered 10 minutes after the model was established. Forty-eight hours later, compared with those administered saline, rabbits receiving SCH79797 showed markedly decreased neuronal damage as assessed by serum neuron specific enolase levels and less neurological dysfunction as determined using cerebral performance category scores. Additionally, in the hippocampus, cell apoptosis, polymorphonuclear cell infiltration, and c-Jun levels were decreased, whereas extracellular signal-regulated kinase phosphorylation levels were increased. All of these changes were inhibited by the intravenous administration of the phosphoinositide 3-kinase/Akt pathway inhibitor LY29004(3 mg/kg) 10 minutes before the SCH79797 intervention. These findings suggest that SCH79797 mitigates brain injury via anti-inflammatory and anti-apoptotic effects, possibly by modulating the extracellular signal-regulated kinase, c-Jun N-terminal kinase/c-Jun and phosphoinositide 3-kinase/Akt pathways.
文摘Initial ischemia/reperfusion injury (IRI) may have an impact on recipient immune responses after transplantation. Allograft inflammatory factor-1 (AIF-1) has been implicated in the regulation of inflammation associated with organ rejection. We hypothesized that it is either passively released from injured tissues during organ procurement, or actively secreted by allograft infiltrating cells contributing to allograft dysfunction. We investigated the impact of IRI in an in vitro study of human heart tissue during the process of transplantation. The mRNA expression levels for both isoforms of the AIF-1, I2 and I3 were significantly increased after 30 minutes reperfusion (AIF-1 I2: p 0.01 vs. AIF-1 I3: p 0.005). Expression levels for IL-18 and the TLRs were increased after 30 minutes of reperfusion. Only IL-18 and TLR-2 were statistically significant (IL-18: p 0.0001 vs. TLR-2: p 0.01). The mRNA expression levels for AIF-1 I2 and IL-18 were decreased from the original levels of ischemia after 60 and 90 minutes reperfusion. The TLR-2 and -4 were presented with minimal levels of reduction after 60 minutes. However, mRNA expression levels for all were decreased to the original levels of ischemia after 90 minutes, except for AIF-1 I3, but the difference was not statistically significant. AIF-1 and IL-18 were specifically detected in myocytes and interstitial tissues by immunohistochemistry (IHC) stain after IRI. TLR-4 was non-specific, and TLR2 was minimally expressed. The study discusses the evidence supporting that the AIF-1 may have therapeutic potential for strategies in the control of innate immune responses early on, after transplantation.
文摘Background: Reduction of myocardial reperfusion injury during cardiopulmonary bypass is an essential requirement for increasing the success rate, decreasing morbidity and mortality of open-heart surgery. Aim: To study the role of pre-operative oral nicorandil in decreasing reperfusion cardiac injury in patients subjected to cardiac valve surgery. Patients and Methods: The study included 62 patients, who were equally randomized into two groups: nicorandil group and control group. Pre-operative, intra-operative and post- operative data were reported and analyzed. Left Ventricle Ejection Fraction (LVEF) was estimated pre-operatively and postoperatively for both groups. Troponin I, creatine kinase-muscle/brain (CK-MB), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured before surgery by 24 hours then 4, 12 and 48 hours after aortic cross clamp removal. Results: Nicorandil considerably decreased TNF-α and IL-6 after 4 and 12 hours following the removal of aortic clamping. It also reduced troponin-I and CKMB at the same time points. However, there were no important changes in IL-6, TNF-α, troponin-I and CK-MB levels in control group in comparison to nicorandil group in the next 48 hours following the removal of aortic clamping. Conclusions: Pre-operative oral nicorandil expressively decreased myocardial reperfusion damage during open heart valve operations, this evidenced by the decrease in the postoperative use of inotropic drugs, considerable reduction of postoperative elevation of cardiac enzymes and inflammatory cytokines with no reported complications.
文摘Hearts of pressure-overload hypertrophy show an increased activation of intracardiac renin-angiotensin system which may contribute to ischemia and reperfusion injury. The purpose of this study is to evaluate whether the hypertrophied myocardium is more vulnerable to ischemia and reperfusion injury and to find out its relation to the cardiac renin-angiotensin system. Hypertrophied rat hearts induced by abdominal aortic banding for 6 weeks were subjected to 2 hours of hypothermic ischemic arrest followed by 30 minutes of reperfusion, and their cardiac function recovery was compared with that of sham-operated normal control hearts. The cardiac renin activity and angiotensin II content before ischemia and after reperfusion were determined. It was found that both the pre-ischemic renin activity and angiotensin II level were higher in hypertrophied myocardium than those in the control: ischemia and reperfusion injury increased both renin activity and angiotensin II content in the two groups, but the renin activity and angiotensin II level were further elevated after reperfusion in the hypertrophied hearts than those in the control hearts. Meanwhile, the cardiac function recovery after 30 minutes reperfusion in the hypertrophied hearts was poorer than that in the control. Correlation analysis revealed that there was a negative correlation between the cardiac output recovery and the myocardial angiotensin II content (r=-0.841), P<0.001), It is concluded that ischemia and reperfusion injury can activate cardiac renin-angiotensin system in isolated rat heart, which may be responsible for the increased susceptibility of the hypertrophied myocardium to ischemia and reperfusion injury.
基金Supported by the National Natural Science Foundation of China (No. 81173514,No.81001673)the Xijing Research Boosting Program (No. XJZT10D02)the Excellent Civil Service Training Fund of Fourth Military Medical University(No. 4138C4IDK6)
文摘OBJECTIVE: To determine the cardioprotective ef- fect of magnesium lithospermate B (MLB) on myo- cardial ischemia/reperfusion (MI/R) injury and to in- vestigate the antioxidant potential in vivo and in vitro. METHODS: MI/R injury was induced by the occlu- sion of left anterior descending coronary artery for 30 min followed by reperfusion for 3 h in rats. After reperfusion, hearts were harvested to assess infarct size, histopathological damages, the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and malondialdehyde (MDA). Blood samples were collected to determine serum levels of creatine kinase-MB (CK-MB), cardiac troponin (cTnl) and lactate dehydrogenase (LDH). Furthermore, simulatedischemia/reperfusion (SI/R) injury in vitro was established by oxygen and glucose deprivation (OGD) for 2 h followed by 24-hour recovery period in cardiomyocytes. The activity of LDH in the cultured su- pernatant and the levels of intracellular reactive oxygen species (ROS), SOD and MDA in cardiomyo- cytes were also measured. Finally, cardiomyocytes apoptosis was determined with flow cytometry. RESULTS: MLB significantly limited infarct size, ameliorated histopathological damages and prevented leakage of CK-MB, cTnl and LDH. Additional- ly, SOD, CAT, GPx and GSH activities were notably increased by MLB, along with the MDA content decreased as compared with the model group in rats. In vitro study, MLB also decreased LDH activity in the cultured supernatant, increased SOD activity in cardiomyocytes, reduced intracellular ROS and MDA levels, and significantly suppressed cardiomyocytes apoptosis. CONCLUSION: MLB possessed remarkably cardioprotective effects on MI/R injury in vivo and in vitro. The protection of MLB may contribute to its antioxidant properties.
文摘BACKGROUND: Resuscitation after cardiac arrest (CA) with a whole-body ischemia–reperfusion injury causes brain injury and multiple organ dysfunction (MODS). This study aimed to determine whether mild systemic hypothermia could decrease multiple organ dysfunctions after resuscitation from cardiac arrest.METHODS: The patients who had been resuscitated after cardiac arrest were reviewed. During the resuscitation they had been assigned to undergo therapeutic hypothermia (target temperature, 32°C to 34°C, measured in the rectum) over a period of 24 to 36 hours or to receive standard treatment with normothermia. Markers of different organ injury were evaluated for the ? rst 72 hours after recovery of spontaneous circulation (ROSC).RESULTS: At 72 hours after ROSC, 23 patients in the hypothermia group for whom data were available had favorable neurologic, myocardial, hepatic and pulmonic outcomes as compared with 26 patients in the normothermia group. The values of renal function were not signi? cantly different between the two groups. However, blood coagulation function was badly injured in the hypothermia group.CONCLUSION: In the patients who have been successfully resuscitated after cardiac arrest, therapeutic mild hypothermia can alleviate dysfunction after resuscitation from cardiac arrest.
文摘Acute interruption of arterial blood flow to the extremities is often associated with significant morbidity and mortality. Broad spectrum mitogenic and non mitogenic activities of FGFs inspired us to study its protecting effects on tissue injuries in ischemia reperfusion condition. We found that systemic administration of aFGF after reperfusion onset prevented severe skeletal muscle injuries. In rats treated with aKGF, the tissue edema was reduced significantly, the tissue viability was increased, and the muscle fibers contained more succinate dehydrogenase (SDH) and adenosine triphosphatasc (ATPase). The pathological results supported the concept of improved prevention with aFGF treatment. The possible tissue protection by aFGF may come from its ability to regulate the concentration of evtra- and intracellular calcium ion. Besides, it may moderate other Ca2+ dependent enzyme conversion processes. Also, it may take part in the vascular tone regulation under ischemia and reperfusion conditions. These results suggest further study of tissue ischemia prevention with FGF and its possible mechanisms in the future.
基金supported by National Basic Research Program of China(2006CB504100,2012CB518200)National Natural Science Foundation(30393130,31071002)+1 种基金Science and Technology committee of Shanghai Municipality(02JC14038)Science and technology program of Hebei province(09276115)
文摘Myocardial ischemia and reperfusion(I/R) is a common problem in clinic and there is no satisfactory method for prevention or treatment of I/R injury so far.Chronic intermittent hypobaric hypoxia(CIHH),similar to the concept of ischemia preconditioning(IPC)or altitude hypoxia adaptation(AHA),has been recognized to confer a protective effect on heart against I/R injury with a longer protective effect than IPC and a less adverse effect than AHA.It has been proved that CIHH increases myocardial tolerance to ischemia or hypoxia,reserving cardiac function and preventing arrhythmia during I/R.Multiple mechanisms or pathway underlying the cardiac protection of CIHH have been proposed,such as induction of heatshock protein,enhancement of myocardial antioxidation capacity,increase of coronary flow and myocardial capillary angiogenesis,activation of adenosine triphosphate(ATP)-sensitive potassium channels,inhibition of mitochondrial permeability transition pores,and activation of protein kinase C(PKC) and induced nitric oxide synthase(iNOS).In addition,CIHH has been found having many beneficial effects on the body,such as promotion of health,increase of oxygen utilization,and prevention or treatment for some diseases.The beneficial effects of CIHH and potential mechanisms are reviewed mainly based on the researches performed by our group.
文摘Purpose: Prevention of myocardial injury is essential during cardiac surgery. Both crystalloid and blood cardioplegia are popular methods for myocardial protection. Most experimental studies have been in favor of blood cardioplegia. The objective of this study is to determine whether the use of warm blood cardioplegia (BCP) is superior to crystalloid cardioplegia (CCP) by means of myocardial injury markers and clinical outcome parameters. Materials and Methods: In a consecutive series of 293 patients, the first 150 received crystalloid cardioplegia, whereas the next 143 patients received blood cardioplegia. Postoperative myocardial injury was assessed by CTnI and CK-MB. Perioperative morbidity and mortality and clinical outcome parameters (need for inotropic support, ICU and hospital stay) were recorded. An unpaired student t-test was performed to analyse continuous postoperative variables relating to myocardial damage. The presence of possible confounders influencing the CTnI or CK-MB concentrations was tested using a student t-test for continuous variables, for categorical variables ANOVA was used. A final longitudinal model was created for CTnI and CK-MB. CTnI was analyzed by a mixed model with random intercept and slope. For all tests performed, statistical significance was 5%. Results: Both groups were well matched with respect to preoperative variables. No significant difference could be found in maximum postoperative levels of CTnI (8.8 ± 18.4 μg/l in BCP vs 9.6 ± 16.5 μg/l in CCP, p = 0.6455) or CK-MB (19.2 ± 31.0 μg/l in BCP vs 26.4 ± 41.5 μg/l in CCP, p = 0.1209). Nor was there any significant difference in other postoperative variables. Testing treatment effect over time proved only significant influence of the surgical intervention type on CTnI levels in time (p < 0.001). Conclusion: This study could not show significantly higher myocardial injury in the group of patients receiving crystalloid cardioplegia versus warm blood cardioplegia. This suggests that warm blood cardioplegia does not confer superior myocardial protection. Surgical intervention type has an important effect on CTnI concentration in time, while the type of cardioplegia does not.
文摘Experimental, clinical and epidemiologic studies have provided strong evidence that physical training has beneficial effects on cardiovascular health. Numerous investigations have demonstrated that exercise increases coronary blood flow and myocardial perfusion. Importantly, training also can stimulate angiogenesis and accelerate collateral vessel growth in animal models with coronary artery occlusion. Cardiac adaptation such as increased vascularity or capillary density has been evidenced after regular endurance exercises. More recently, several studies indicate that physical training induces high levels of myocardial heat shock protein and antioxidant protein expression, which may play an important role in myocardial protection against ischemia-reperfusion injury.