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
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
In the present paper, effects of electroacupuncture (EA) of 3 points of the Heart Meridian and other 3 points of the Lung Meridian on changes of electrocardiogram (ECG), small intestinal electrogram (SIG) and electroe...In the present paper, effects of electroacupuncture (EA) of 3 points of the Heart Meridian and other 3 points of the Lung Meridian on changes of electrocardiogram (ECG), small intestinal electrogram (SIG) and electroencephalogram (EEG) in intravenous drip of pituitrin induced myocardial ischemia rabbits. The three points of the Heart Meridian are "Shenmen" (HT 7), "Lingdao" (HT 4) and one point between HT 7 and HT 4, the 3 points of the Lung Meridian are "Taiyuan"(LU 9), Lieque (LU 7) and one point between LU 9 and LU 7. These points are punctured with filiform needles and stimulated electrically by setting the parameters being frequency of 2.5 Hz, dense sparse waves and duration of 10 min. Results display that the regulative effect of EA of the Heart Meridian is superior to that of EA of the Lung Meridian on the three indexes, showing a closer correlation between the whole Heart Meridian and activities of ECG, SIG and EEG.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
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
The effect of myocardium being subjected to 60 min ischemia and 60 min reperfusion incat cardiopulmonary bypass on level of lipid peroxides(LPO),function of myocardial mitochon-dria and activity of superoxides dismuta...The effect of myocardium being subjected to 60 min ischemia and 60 min reperfusion incat cardiopulmonary bypass on level of lipid peroxides(LPO),function of myocardial mitochon-dria and activity of superoxides dismutase(SOD)was studied. Myocardial mitochondrial functionwas depressed slightly 60 rain after ischemia but significantly 60 min after reperfusion.Increasedlipid peroxides content and decreased activity of SOD were observed at 60 rain after ischemia.Af-ter reperfusion,the activity of SOD continued decreasing,and LPO elevated still further.Theseresults support the hypothesis that free radicals may contribute to myocardial 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
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.
文摘In the present paper, effects of electroacupuncture (EA) of 3 points of the Heart Meridian and other 3 points of the Lung Meridian on changes of electrocardiogram (ECG), small intestinal electrogram (SIG) and electroencephalogram (EEG) in intravenous drip of pituitrin induced myocardial ischemia rabbits. The three points of the Heart Meridian are "Shenmen" (HT 7), "Lingdao" (HT 4) and one point between HT 7 and HT 4, the 3 points of the Lung Meridian are "Taiyuan"(LU 9), Lieque (LU 7) and one point between LU 9 and LU 7. These points are punctured with filiform needles and stimulated electrically by setting the parameters being frequency of 2.5 Hz, dense sparse waves and duration of 10 min. Results display that the regulative effect of EA of the Heart Meridian is superior to that of EA of the Lung Meridian on the three indexes, showing a closer correlation between the whole Heart Meridian and activities of ECG, SIG and EEG.
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.
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The effect of myocardium being subjected to 60 min ischemia and 60 min reperfusion incat cardiopulmonary bypass on level of lipid peroxides(LPO),function of myocardial mitochon-dria and activity of superoxides dismutase(SOD)was studied. Myocardial mitochondrial functionwas depressed slightly 60 rain after ischemia but significantly 60 min after reperfusion.Increasedlipid peroxides content and decreased activity of SOD were observed at 60 rain after ischemia.Af-ter reperfusion,the activity of SOD continued decreasing,and LPO elevated still further.Theseresults support the hypothesis that free radicals may contribute to myocardial 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.
