BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary ...BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will benefit the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs. METHODS: One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8) controls 1, 2 and 3 (C-1, C-2, C-3, n=16), and experimental 1, 2 and 3 (E-1, E-2, E-3, n=16). For groups C-1 and E-1, C-2 and E-2, and C-3 and E-3, the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were flushed with and preserved in 4 degrees C Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation. RESULTS: At I hour after portal vein reperfusion, the levels of NO in groups E-1, E-2, E-3 and C-1, C-2, C-3 were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P<0.05). At 1, 3, and 24 hours, the levels of NO in groups E-1, E-2, E-3 were higher, while the levels of plasma ET, serum ALT and AST were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of NO in groups C-2 and C-3 were lower than in group C-1 (P<0.05), and the level of NO in group C-3 was lower than in group C-2 (P<0.05). At 1, 3 and 24 hours, the levels of plasma ET, serum ALT, and AST in groups E-1, E-2, E-3 were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of plasma ET, serum ALT, and AST were lower in group C-3 than in groups C-1 and C-2 (P<0.05). Pathological changes in groups E-1, E-2, E-3 were milder than those in the corresponding experimental control groups (C-1, C-2, C-3). CONCLUSIONS: The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.展开更多
Summary： This study was designed to investigate the cardioprotective effects of preconditioning with 3-nitropropionic acid, an inhibitor of mitochondrial succinate dehydrogenase. 16 isolated rat hearts were randomly ...Summary： This study was designed to investigate the cardioprotective effects of preconditioning with 3-nitropropionic acid, an inhibitor of mitochondrial succinate dehydrogenase. 16 isolated rat hearts were randomly divided into two groups, a treatment group and a control group. The rats of the treatment group were treated intraperitoneally with 3-nitropropionic ac;.d （3-NPA, 4 mg/kg） and the rats of the control group were treated with saline. 24 h after the treatment, the isolated hearts were mounted on a Langendorff apparatus. After 30 min, the hearts were subjected to 30min ischemia and 60-min reperfusion. The HR, LVDP and ±dp/dtmax were measured at preischemia and 30 min, 60 min after the reperfusion. Coronary effluent was collected 15 min after the reperfusion for the determination of CK and LDH. At the end of the 60-min reperfusion the heart was removed for the determination of myocardial SOD and MDA. Our results showed that in the 3-NPA group LVDP and ±dp/dt recovered significantly better, myocardial MDA, CK and LDH were significantly lower and the myocardial SOD was significantly higher than in the control group. It is concluded that chemical preconditioning by 3-nitropropionate has cardioprotective effects against ischemia-reperfusion injury.展开更多
Objectives: We hypothesized that the organisms and their organs or tissues could adapt themselves to the gradual changes of environment for surviving or reducing damage. This study explored whether gradual clamping (G...Objectives: We hypothesized that the organisms and their organs or tissues could adapt themselves to the gradual changes of environment for surviving or reducing damage. This study explored whether gradual clamping (GC) could reduce myocardial ischemia-reperfusion (IR) injury in rat heart. Methods: Twelve rats were randomized to IR group and GC group, then the hearts were isolated and perfused with Langendorff apparatus. Before cardioplegia, the perfusion was stopped abruptly in IR group while slowly with 5-minute in GC group. The hearts were subjected to 30-minute ischemia and 60-minute reperfusion. The left ventricular develop pressure (LVDP) and systolic pressure (LVSP), the maximal rate of the increase and decrease of left ventricular pressure (+dp/dt<sub>max</sub>, ﹣dp/dt<sub>max</sub>) were measured by polygraph system at different time points. The recovery of the variables was expressed as the ratio of these values at individual time point after reperfusion to the baseline respectively. Results: The recovery of LVDP after reperfusion was better than that in IR group (P = 0.034). No significant difference in the recovery of LVSP, +dp/dtmax and ﹣dp/dt<sub>max</sub> between groups was observed. Conclusions: Gradual clamping could improve the recovery of LVDP after IR, suggesting that gradual clamping could reduce myocardial IR injury.展开更多
Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury ...Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.展开更多
This work was designed to explore efficacy of apelin-12 (A-12) as a cardioprotective agent when given before ischemia or at reperfusion using the isolated working heart model. Hearts of male Wistar rats were subjected...This work was designed to explore efficacy of apelin-12 (A-12) as a cardioprotective agent when given before ischemia or at reperfusion using the isolated working heart model. Hearts of male Wistar rats were subjected to 30-min stabilization period followed by 35-min global ischemia and 30-min reperfusion. A short-term infusion of Krebs-Henseleit buffer (KHB) con-taining A-12 (35, 70, 140, 280 or 560 ?M) was ap-plied prior to ischemia (A-12-I) or at onset of reperfusion (A-12-R). KHB infusion was used as control. A-12 infusions induced a dose-dependent increase in recovery of coronary flow, contractile and pump function during reperfu-sion, with the largest augmentation of these indices in the A-12-I group. Both A-12 groups exhibited a significant reduction of LV diastolic pressure rise during reperfusion compared with control. Enhanced functional recovery in the A-12-I group was combined with a decrease in LDH leakage in perfusate on early reperfusion (by 36% vs. control, p < 0.05). Preischemic infusion of 140 ?M A-12 markedly increased myocardial ATP content, enhanced preservation of the total adenine nucleotide pool and improved recovery of the energy charge in reperfused hearts. There was a trend towards increase in myocardial phosphocreatine by the end of re- perfusion in the A-12-I group;however this benefit did not reach statistical significance. At the end of reperfusion, myocardial lactate and lactate/pyruvate ratio were on average 5-fold lower in A-12-I treated hearts compared with control ones and did not differ significantly from the initial values. Therefore, improved cardiac dysfunction after I/R injury and less cell mem-brane damage induced by A-12 are associated with maintaining high energy phosphates, particularly ATP, in reperfused myocardium. Changes in energy metabolism may play a role in mechanisms of cardioprotection afforded by A-12 during I/R stress.展开更多
Early reperfusion of ischemic cardiac tissue is usually the best option to improve clinical outcome of angina pectoris, especially of acute myocardial infarction. However, myocardial reperfusion may cause an abnormal ...Early reperfusion of ischemic cardiac tissue is usually the best option to improve clinical outcome of angina pectoris, especially of acute myocardial infarction. However, myocardial reperfusion may cause an abnormal increase of intracellular Ca^2+-mediated cardiomyocyte death and consequent loss of cardiac function, which is referred to myocardial ischemia/reperfusion (I/R) injury. Recently, the microRNA-214 (miR-214)/Na^+/Ca^2+ exchanger (NCX) 1 co-expression is a key factor in cellular protection against myocardial apoptosis for myocardial I/R injury. Once activated, miR-214/NCX1 axis can inhibit several Ca^2+ downstream signaling effectors that mediate cell death simultaneously. Studies have shown that acupuncture preconditioning has a protective effect on myocardial I/R injury, but its mechanism deserves further research. It has been proved that acupuncture preconditioning for ischemic myocardium successfully inhibit multiple Ca2+ handling related microRNAs that mediate cell death pathways, and miR-214 is one of its targets. In terms of clinical practice, coronary heart disease (CHD) patients benefit a lot from this intervention. However, there is barely no study correlating acupuncture preconditioning to the miR-214/NCX1 co-expression in patients with CHD. This review aims to discuss whether there is some evidence to justify a recommendation of acupuncture preconditioning in CHD patients as a non-pharmacological therapeutic method to activate the miR-214/NCX1 co-expression network model.展开更多
基金a grant from the Science & Technology Development Foundation of Guangdong Health Bureau(No.2006345).
文摘BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will benefit the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs. METHODS: One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8) controls 1, 2 and 3 (C-1, C-2, C-3, n=16), and experimental 1, 2 and 3 (E-1, E-2, E-3, n=16). For groups C-1 and E-1, C-2 and E-2, and C-3 and E-3, the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were flushed with and preserved in 4 degrees C Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation. RESULTS: At I hour after portal vein reperfusion, the levels of NO in groups E-1, E-2, E-3 and C-1, C-2, C-3 were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P<0.05). At 1, 3, and 24 hours, the levels of NO in groups E-1, E-2, E-3 were higher, while the levels of plasma ET, serum ALT and AST were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of NO in groups C-2 and C-3 were lower than in group C-1 (P<0.05), and the level of NO in group C-3 was lower than in group C-2 (P<0.05). At 1, 3 and 24 hours, the levels of plasma ET, serum ALT, and AST in groups E-1, E-2, E-3 were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of plasma ET, serum ALT, and AST were lower in group C-3 than in groups C-1 and C-2 (P<0.05). Pathological changes in groups E-1, E-2, E-3 were milder than those in the corresponding experimental control groups (C-1, C-2, C-3). CONCLUSIONS: The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.
文摘Summary： This study was designed to investigate the cardioprotective effects of preconditioning with 3-nitropropionic acid, an inhibitor of mitochondrial succinate dehydrogenase. 16 isolated rat hearts were randomly divided into two groups, a treatment group and a control group. The rats of the treatment group were treated intraperitoneally with 3-nitropropionic ac;.d （3-NPA, 4 mg/kg） and the rats of the control group were treated with saline. 24 h after the treatment, the isolated hearts were mounted on a Langendorff apparatus. After 30 min, the hearts were subjected to 30min ischemia and 60-min reperfusion. The HR, LVDP and ±dp/dtmax were measured at preischemia and 30 min, 60 min after the reperfusion. Coronary effluent was collected 15 min after the reperfusion for the determination of CK and LDH. At the end of the 60-min reperfusion the heart was removed for the determination of myocardial SOD and MDA. Our results showed that in the 3-NPA group LVDP and ±dp/dt recovered significantly better, myocardial MDA, CK and LDH were significantly lower and the myocardial SOD was significantly higher than in the control group. It is concluded that chemical preconditioning by 3-nitropropionate has cardioprotective effects against ischemia-reperfusion injury.
文摘Objectives: We hypothesized that the organisms and their organs or tissues could adapt themselves to the gradual changes of environment for surviving or reducing damage. This study explored whether gradual clamping (GC) could reduce myocardial ischemia-reperfusion (IR) injury in rat heart. Methods: Twelve rats were randomized to IR group and GC group, then the hearts were isolated and perfused with Langendorff apparatus. Before cardioplegia, the perfusion was stopped abruptly in IR group while slowly with 5-minute in GC group. The hearts were subjected to 30-minute ischemia and 60-minute reperfusion. The left ventricular develop pressure (LVDP) and systolic pressure (LVSP), the maximal rate of the increase and decrease of left ventricular pressure (+dp/dt<sub>max</sub>, ﹣dp/dt<sub>max</sub>) were measured by polygraph system at different time points. The recovery of the variables was expressed as the ratio of these values at individual time point after reperfusion to the baseline respectively. Results: The recovery of LVDP after reperfusion was better than that in IR group (P = 0.034). No significant difference in the recovery of LVSP, +dp/dtmax and ﹣dp/dt<sub>max</sub> between groups was observed. Conclusions: Gradual clamping could improve the recovery of LVDP after IR, suggesting that gradual clamping could reduce myocardial IR injury.
基金Supported by the National Natural Science Foundation of China(Nos.30700884,30873145)the Distinguished Middle-aged and Young Scientist Encourage and Reward Foundation of Shandong Province,China(No.BS2009SW015)
文摘Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.
文摘This work was designed to explore efficacy of apelin-12 (A-12) as a cardioprotective agent when given before ischemia or at reperfusion using the isolated working heart model. Hearts of male Wistar rats were subjected to 30-min stabilization period followed by 35-min global ischemia and 30-min reperfusion. A short-term infusion of Krebs-Henseleit buffer (KHB) con-taining A-12 (35, 70, 140, 280 or 560 ?M) was ap-plied prior to ischemia (A-12-I) or at onset of reperfusion (A-12-R). KHB infusion was used as control. A-12 infusions induced a dose-dependent increase in recovery of coronary flow, contractile and pump function during reperfu-sion, with the largest augmentation of these indices in the A-12-I group. Both A-12 groups exhibited a significant reduction of LV diastolic pressure rise during reperfusion compared with control. Enhanced functional recovery in the A-12-I group was combined with a decrease in LDH leakage in perfusate on early reperfusion (by 36% vs. control, p < 0.05). Preischemic infusion of 140 ?M A-12 markedly increased myocardial ATP content, enhanced preservation of the total adenine nucleotide pool and improved recovery of the energy charge in reperfused hearts. There was a trend towards increase in myocardial phosphocreatine by the end of re- perfusion in the A-12-I group;however this benefit did not reach statistical significance. At the end of reperfusion, myocardial lactate and lactate/pyruvate ratio were on average 5-fold lower in A-12-I treated hearts compared with control ones and did not differ significantly from the initial values. Therefore, improved cardiac dysfunction after I/R injury and less cell mem-brane damage induced by A-12 are associated with maintaining high energy phosphates, particularly ATP, in reperfused myocardium. Changes in energy metabolism may play a role in mechanisms of cardioprotection afforded by A-12 during I/R stress.
基金the Natural Science Foundation of Inner Mongolia Autonomous Region in China (Grant No.2018MS08043)the National Natural Science Foundation of China (Grant No.81573885)+1 种基金Project of Huhhot Science and Technology (Grant No.2018-Sociology-1-3)Research Project of Health and Family Planning Commission of Inner Mongolia in China (Grant No.201703145).
文摘Early reperfusion of ischemic cardiac tissue is usually the best option to improve clinical outcome of angina pectoris, especially of acute myocardial infarction. However, myocardial reperfusion may cause an abnormal increase of intracellular Ca^2+-mediated cardiomyocyte death and consequent loss of cardiac function, which is referred to myocardial ischemia/reperfusion (I/R) injury. Recently, the microRNA-214 (miR-214)/Na^+/Ca^2+ exchanger (NCX) 1 co-expression is a key factor in cellular protection against myocardial apoptosis for myocardial I/R injury. Once activated, miR-214/NCX1 axis can inhibit several Ca^2+ downstream signaling effectors that mediate cell death simultaneously. Studies have shown that acupuncture preconditioning has a protective effect on myocardial I/R injury, but its mechanism deserves further research. It has been proved that acupuncture preconditioning for ischemic myocardium successfully inhibit multiple Ca2+ handling related microRNAs that mediate cell death pathways, and miR-214 is one of its targets. In terms of clinical practice, coronary heart disease (CHD) patients benefit a lot from this intervention. However, there is barely no study correlating acupuncture preconditioning to the miR-214/NCX1 co-expression in patients with CHD. This review aims to discuss whether there is some evidence to justify a recommendation of acupuncture preconditioning in CHD patients as a non-pharmacological therapeutic method to activate the miR-214/NCX1 co-expression network model.
