Tumour necrosis factor-α is a cytokine released during myocardial infarction. According to the literature, the effect of TNFα on myocardial infarction is controversial, especially when administered before the ischem...Tumour necrosis factor-α is a cytokine released during myocardial infarction. According to the literature, the effect of TNFα on myocardial infarction is controversial, especially when administered before the ischemic period. The deleterious effects of TNFα seem to be related to the triggering of apoptosis. This study has been designed to determine if different doses of TNFα, administered before the ischemic period, have the same effect on infarct size and on activation of caspase-3 and-8, two enzymes involved in apoptosis. Four groups, using a porcine model of myocardial infarction, have been used: placebo and TNFα (0.1 μg/kg;1 μg/kg and 3 μg/kg). All administered 15 minutes before a 50 minutes occlusion of the left anterior descending artery. Myocardial infarct size has been determined at 3 hours of reperfusion. In a subgroup of animals, reperfusion period has been limited to 15 min to determine the activity of caspase-3 and-8 by spectrofluorometry. Results indicated that infarct size is significantly smaller in groups 0.1 μg/kg and 1 μg/ kg as compared to the placebo group. In contrast, the 3 μg/kg group presented an infarct size similar to the placebo group. Activity of caspase-3 and-8 is reduced in the ischemic region in groups 0.1 and 1 μg/ kg as compared to the placebo group whereas activity in the 3 μg/kg group was similar to the placebo. The results obtained indicated that a low dose of TNFα administered before the ischemic period reduces infarct size, whereas the cardioprotection is lost with the high dose.展开更多
Previous studies have shown that nicorandil has a protective effect on cardiomyocytes.However,there is no study to investigate whether perioperative intravenous nicorandil can further reduce the myocardial infarct siz...Previous studies have shown that nicorandil has a protective effect on cardiomyocytes.However,there is no study to investigate whether perioperative intravenous nicorandil can further reduce the myocardial infarct size in patients with ST-segment elevation myocardial infarction(STEMI)compared to the current standard of percutaneous coronary intervention(PCI)regimen.The CHANGE(China-Administration of Nicorandil Group)study is a multicenter,prospective,randomized,double-blind and parallel-controlled clinical study of STEMI patients undergoing primary PCI in China,aiming to evaluate the efficacy and safety of intravenous nicorandil in ameliorating the myocardial infarct size in STEMI patients undergoing primary PCI and provide evidence-based support for myocardial protection strategies of STEMI patients.展开更多
BACKGROUND:Intravenous transplantation has been regarded as a most safe method in stem cell therapies.There is evidence showing the homing of bone marrow stem cells(BMSCs) into the injured sites,and thus these cells c...BACKGROUND:Intravenous transplantation has been regarded as a most safe method in stem cell therapies.There is evidence showing the homing of bone marrow stem cells(BMSCs) into the injured sites,and thus these cells can be used in the treatment of acute myocardial infarction(Ml).This study aimed to investigate the effect of intravenous and epicardial transplantion of BMSCs on myocardial infarction size in a rabbit model.METHODS:A total of 60 New Zealand rabbits were randomly divided into three groups:control group,epicardium group(group Ⅰ) and ear vein group(group Ⅱ).The BMSCs were collected from the tibial plateau in group Ⅰ and group Ⅱ,cultured and labeled.In the three groups,rabbits underwent thoracotomy and ligation of the middle left anterior descending artery.The elevation of ST segment>0.2 mV lasting for 30 minutes on the lead Ⅱ and Ⅲ of electrocardiogram suggested successful introduction of myocardial infarction.Two weeks after myocardial infarction,rabbits in group Ⅰ were treated with autogenous BMSCs at the infarct region and those in group Ⅱ received intravenous transplantation of BMSCs.In the control group,rabbits were treated with PBS following thoracotomy.Four weeks after myocardial infarction,the heart was collected from all rabbits and the infarct size was calculated.The heart was cut into sections followed by HE staining and calculation of infarct size with an image system.RESULTS:In groups Ⅰ and Ⅱ,the infarct size was significantly reduced after transplantation with BMSCs when compared with the control group(P<0.05).However,there was no significant difference in the infarct size between groups Ⅰ and Ⅱ(P>0.05).CONCLUSION:Transplantation of BMSCs has therapeutic effect on Ml.Moreover,epicardial and intravenous transplantation of BMSCs has comparable therapeutic efficacy on myocardial infarction.展开更多
AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar...AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.展开更多
In patients with an acute ST-segment elevation myocardial infarction, timely myocardial reperfusion using primary percutaneous coronary intervention is the most effective therapy for limiting myocardial infarct size, ...In patients with an acute ST-segment elevation myocardial infarction, timely myocardial reperfusion using primary percutaneous coronary intervention is the most effective therapy for limiting myocardial infarct size, preserving left-ventricular systolic function and reducing the onset of heart failure. Within minutes after the restoration of blood flow, however, reperfusion itself results in additional damage, also known as myocardial ischemia-reperfusion injury. An improved understanding of the pathophysiological mechanisms underlying reperfusion injury has resulted in the identification ofseveral promising pharmacological(cyclosporin-A, exenatide, glucose-insulin-potassium, atrial natriuretic peptide, adenosine, abciximab, erythropoietin, metoprolol and melatonin) therapeutic strategies for reducing the severity of myocardial reperfusion injury. Many of these agents have shown promise in initial proofof-principle clinical studies. In this article, we review the pathophysiology underlying myocardial reperfusion injury and highlight the potential pharmacological interventions which could be used in the future to prevent reperfusion injury and improve clinical outcomes in patients with coronary heart disease.展开更多
Objective Previous studies showed that hypoxia preconditioning could protect cardiac function against subsequent myo-cardial infarction injury. However, the effect of hypoxia on left ventricular after myocardial infar...Objective Previous studies showed that hypoxia preconditioning could protect cardiac function against subsequent myo-cardial infarction injury. However, the effect of hypoxia on left ventricular after myocardial infarction is still unclear. This study therefore aims to investigate the effects of hypoxia training on left ventricular remodeling in rabbits post myocardial infarction. Methods Adult male rabbits were randomly divided into three groups： group SO （sham operated）, group MI （myocardial infarc-tion only） and group MI-HT （myocardial infarction plus hypoxia training）. Myocardial infarction was induced by left ventricular branch ligation. Hypoxia training was performed in a hypobaric chamber （having equivalent condition at an altitude of 4000 m, FiO214.9%） for 1 h/day, 5 days/week for four weeks. At the endpoints, vascular endothelial growth factor （VEGF） in the plasma was measured. Infarct size and capillary density were detected by histology. Left ventricular remodeling and function were as-sessed by echocardiography.Results After the 4-week experiment, compared with the group SO, plasma VEGF levels in groups MI （130.27 ± 18.58 pg/mL,P〈 0.01） and MI-HT （181.93 ± 20.29 pg/mL,P〈 0.01） were significantly increased. Infarct size in Group MI-HT （29.67% ± 7.73%） was deceased remarkably, while its capillary density （816.0 ± 122.2/mm2） was significantly increased. For both groups MI and MI-HT, left ventricular end-diastolic and end-systolic dimensions were increased whereas left ventricular ejection fraction was decreased. However, compared with group MI, group MI-HT diminished left ventricular end-diastolic （15.86 ± 1.09 mm,P〈 0.05） and end-systolic dimensions （12.10 ± 1.20 mm,P〈 0.01） significantly and im-proved left ventricular ejection fraction （54.39 ± 12.74 mm,P〈 0.05）.ConclusionHypoxia training may improve left ven-tricular function and reduce remodeling via angiogenesis in rabbits with MI.展开更多
Background: Cardiac complications after myocardial infarction are believed to be worse in the presence of comorbidities;we tested whether experimentally induced prolonged uremia exacer-bated myocardial necrosis in a r...Background: Cardiac complications after myocardial infarction are believed to be worse in the presence of comorbidities;we tested whether experimentally induced prolonged uremia exacer-bated myocardial necrosis in a rabbit preparation of ischemia-reperfusion injury. In addition, we examined if treatment with an angiotensin converting enzyme inhibitor (Enalapril, ENA, 3 mg/Kg, IV) could reduce post-ischemic myocardial damage. Methods: Prolonged uremia was induced by a two-stage subtotal nephrectomy and confirmed by marked increases in serum creatinine and urea levels;after 5 weeks, four groups of rabbits were exposed to 45-min acute coronary occlusion followed by 180-min reperfusion. In treated animals, ENA was administered 5-min before onset of coronary reperfusion. All data from uremic animals were compared with time-matched controls. Results: Cardiac hemodynamics was similar for all groups during the development of kidney failure;heart rate in uremic rabbits was significantly lower for the duration of ischemia-reperfusion. In this animal model, the absence of coronary collateral circulation provides a stable ischemic substrate for evaluation of cellular necrosis. Infarct size (expressed as percent risk zone size) was: control, 48 ± 16;uremia, 36 ± 5;control + ENA, 51 ± 19;and uremia + ENA, 41 ± 16;risk zone size was similar for all animals. Conclusion: The present findings are inconsistent with the view that post-ischemic cardiac injury is greater in animals with pre-existent uremia. In addition, we were unable to show a significant beneficial effect with an angiotensin converting enzyme inhibitor on infarct size in either control or uremic rabbits. It remains to be proven in animal models with comorbidities such as manifest kidney disease that ischemic tolerance can be substantially reduced by either pharmacologic or non-pharmacologic interventions.展开更多
Primary coronary revascularization by means of percutaneous coronary intervention(PCI)is a highly effective treatment of acute myocardial infarction re-establishing coronary perfusion and stopping the ongoing necrosis...Primary coronary revascularization by means of percutaneous coronary intervention(PCI)is a highly effective treatment of acute myocardial infarction re-establishing coronary perfusion and stopping the ongoing necrosis in the dependent myocardium.Single-photon emission computed tomography(SPECT)is the most widely used modality assessing myocardial salvage as the difference between the acute perfusion defect before intervention and the remaining scar size measured in a second scan several days after the event.SPECT allows quantification of area at risk(AAR)and final infarct size(FIS)by tracer injection prior to revascularization and after 1 month,respectively.SPECT provides the most validated measure of myocardial salvage and has been utilized in multiple randomizedclinical trials.However,SPECT is logistically challenging,expensive,and includes radiation exposure.More recently,a large number of studies have suggested that cardiac magnetic resonance(CMR)can determine salvage in a single examination by combining measures of myocardial oedema in the AAR exposed to ischaemia reperfusion with FIS quantification by late gadolinium enhancement.展开更多
文摘Tumour necrosis factor-α is a cytokine released during myocardial infarction. According to the literature, the effect of TNFα on myocardial infarction is controversial, especially when administered before the ischemic period. The deleterious effects of TNFα seem to be related to the triggering of apoptosis. This study has been designed to determine if different doses of TNFα, administered before the ischemic period, have the same effect on infarct size and on activation of caspase-3 and-8, two enzymes involved in apoptosis. Four groups, using a porcine model of myocardial infarction, have been used: placebo and TNFα (0.1 μg/kg;1 μg/kg and 3 μg/kg). All administered 15 minutes before a 50 minutes occlusion of the left anterior descending artery. Myocardial infarct size has been determined at 3 hours of reperfusion. In a subgroup of animals, reperfusion period has been limited to 15 min to determine the activity of caspase-3 and-8 by spectrofluorometry. Results indicated that infarct size is significantly smaller in groups 0.1 μg/kg and 1 μg/ kg as compared to the placebo group. In contrast, the 3 μg/kg group presented an infarct size similar to the placebo group. Activity of caspase-3 and-8 is reduced in the ischemic region in groups 0.1 and 1 μg/ kg as compared to the placebo group whereas activity in the 3 μg/kg group was similar to the placebo. The results obtained indicated that a low dose of TNFα administered before the ischemic period reduces infarct size, whereas the cardioprotection is lost with the high dose.
基金supported by the National Key Research and Development program of China(2018ZX09201013)Xinxin Merck Cardiovascular Research Fund(2017-CCA-xinxin merck fund-003)。
文摘Previous studies have shown that nicorandil has a protective effect on cardiomyocytes.However,there is no study to investigate whether perioperative intravenous nicorandil can further reduce the myocardial infarct size in patients with ST-segment elevation myocardial infarction(STEMI)compared to the current standard of percutaneous coronary intervention(PCI)regimen.The CHANGE(China-Administration of Nicorandil Group)study is a multicenter,prospective,randomized,double-blind and parallel-controlled clinical study of STEMI patients undergoing primary PCI in China,aiming to evaluate the efficacy and safety of intravenous nicorandil in ameliorating the myocardial infarct size in STEMI patients undergoing primary PCI and provide evidence-based support for myocardial protection strategies of STEMI patients.
基金supported by grants from the Scientific Research Plan Project of Liaoning Province(20092250096)Scientific Research Plan Project of Dalian(2010E15SF178)
文摘BACKGROUND:Intravenous transplantation has been regarded as a most safe method in stem cell therapies.There is evidence showing the homing of bone marrow stem cells(BMSCs) into the injured sites,and thus these cells can be used in the treatment of acute myocardial infarction(Ml).This study aimed to investigate the effect of intravenous and epicardial transplantion of BMSCs on myocardial infarction size in a rabbit model.METHODS:A total of 60 New Zealand rabbits were randomly divided into three groups:control group,epicardium group(group Ⅰ) and ear vein group(group Ⅱ).The BMSCs were collected from the tibial plateau in group Ⅰ and group Ⅱ,cultured and labeled.In the three groups,rabbits underwent thoracotomy and ligation of the middle left anterior descending artery.The elevation of ST segment>0.2 mV lasting for 30 minutes on the lead Ⅱ and Ⅲ of electrocardiogram suggested successful introduction of myocardial infarction.Two weeks after myocardial infarction,rabbits in group Ⅰ were treated with autogenous BMSCs at the infarct region and those in group Ⅱ received intravenous transplantation of BMSCs.In the control group,rabbits were treated with PBS following thoracotomy.Four weeks after myocardial infarction,the heart was collected from all rabbits and the infarct size was calculated.The heart was cut into sections followed by HE staining and calculation of infarct size with an image system.RESULTS:In groups Ⅰ and Ⅱ,the infarct size was significantly reduced after transplantation with BMSCs when compared with the control group(P<0.05).However,there was no significant difference in the infarct size between groups Ⅰ and Ⅱ(P>0.05).CONCLUSION:Transplantation of BMSCs has therapeutic effect on Ml.Moreover,epicardial and intravenous transplantation of BMSCs has comparable therapeutic efficacy on myocardial infarction.
基金Supported by Russian Science Foundation,No.17-75-30052
文摘AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.
基金Supported by Framework of one research project of the Spanish Society of Cardiology for Clinical Research in Cardiology 2012
文摘In patients with an acute ST-segment elevation myocardial infarction, timely myocardial reperfusion using primary percutaneous coronary intervention is the most effective therapy for limiting myocardial infarct size, preserving left-ventricular systolic function and reducing the onset of heart failure. Within minutes after the restoration of blood flow, however, reperfusion itself results in additional damage, also known as myocardial ischemia-reperfusion injury. An improved understanding of the pathophysiological mechanisms underlying reperfusion injury has resulted in the identification ofseveral promising pharmacological(cyclosporin-A, exenatide, glucose-insulin-potassium, atrial natriuretic peptide, adenosine, abciximab, erythropoietin, metoprolol and melatonin) therapeutic strategies for reducing the severity of myocardial reperfusion injury. Many of these agents have shown promise in initial proofof-principle clinical studies. In this article, we review the pathophysiology underlying myocardial reperfusion injury and highlight the potential pharmacological interventions which could be used in the future to prevent reperfusion injury and improve clinical outcomes in patients with coronary heart disease.
基金We are grateful to the support of Dr. Lei Yuan and Shao-Shao Zhao for their technical assistance. This work was supported in part by China Postdoctoral Science Foundation Province, China
文摘Objective Previous studies showed that hypoxia preconditioning could protect cardiac function against subsequent myo-cardial infarction injury. However, the effect of hypoxia on left ventricular after myocardial infarction is still unclear. This study therefore aims to investigate the effects of hypoxia training on left ventricular remodeling in rabbits post myocardial infarction. Methods Adult male rabbits were randomly divided into three groups： group SO （sham operated）, group MI （myocardial infarc-tion only） and group MI-HT （myocardial infarction plus hypoxia training）. Myocardial infarction was induced by left ventricular branch ligation. Hypoxia training was performed in a hypobaric chamber （having equivalent condition at an altitude of 4000 m, FiO214.9%） for 1 h/day, 5 days/week for four weeks. At the endpoints, vascular endothelial growth factor （VEGF） in the plasma was measured. Infarct size and capillary density were detected by histology. Left ventricular remodeling and function were as-sessed by echocardiography.Results After the 4-week experiment, compared with the group SO, plasma VEGF levels in groups MI （130.27 ± 18.58 pg/mL,P〈 0.01） and MI-HT （181.93 ± 20.29 pg/mL,P〈 0.01） were significantly increased. Infarct size in Group MI-HT （29.67% ± 7.73%） was deceased remarkably, while its capillary density （816.0 ± 122.2/mm2） was significantly increased. For both groups MI and MI-HT, left ventricular end-diastolic and end-systolic dimensions were increased whereas left ventricular ejection fraction was decreased. However, compared with group MI, group MI-HT diminished left ventricular end-diastolic （15.86 ± 1.09 mm,P〈 0.05） and end-systolic dimensions （12.10 ± 1.20 mm,P〈 0.01） significantly and im-proved left ventricular ejection fraction （54.39 ± 12.74 mm,P〈 0.05）.ConclusionHypoxia training may improve left ven-tricular function and reduce remodeling via angiogenesis in rabbits with MI.
文摘Background: Cardiac complications after myocardial infarction are believed to be worse in the presence of comorbidities;we tested whether experimentally induced prolonged uremia exacer-bated myocardial necrosis in a rabbit preparation of ischemia-reperfusion injury. In addition, we examined if treatment with an angiotensin converting enzyme inhibitor (Enalapril, ENA, 3 mg/Kg, IV) could reduce post-ischemic myocardial damage. Methods: Prolonged uremia was induced by a two-stage subtotal nephrectomy and confirmed by marked increases in serum creatinine and urea levels;after 5 weeks, four groups of rabbits were exposed to 45-min acute coronary occlusion followed by 180-min reperfusion. In treated animals, ENA was administered 5-min before onset of coronary reperfusion. All data from uremic animals were compared with time-matched controls. Results: Cardiac hemodynamics was similar for all groups during the development of kidney failure;heart rate in uremic rabbits was significantly lower for the duration of ischemia-reperfusion. In this animal model, the absence of coronary collateral circulation provides a stable ischemic substrate for evaluation of cellular necrosis. Infarct size (expressed as percent risk zone size) was: control, 48 ± 16;uremia, 36 ± 5;control + ENA, 51 ± 19;and uremia + ENA, 41 ± 16;risk zone size was similar for all animals. Conclusion: The present findings are inconsistent with the view that post-ischemic cardiac injury is greater in animals with pre-existent uremia. In addition, we were unable to show a significant beneficial effect with an angiotensin converting enzyme inhibitor on infarct size in either control or uremic rabbits. It remains to be proven in animal models with comorbidities such as manifest kidney disease that ischemic tolerance can be substantially reduced by either pharmacologic or non-pharmacologic interventions.
文摘Primary coronary revascularization by means of percutaneous coronary intervention(PCI)is a highly effective treatment of acute myocardial infarction re-establishing coronary perfusion and stopping the ongoing necrosis in the dependent myocardium.Single-photon emission computed tomography(SPECT)is the most widely used modality assessing myocardial salvage as the difference between the acute perfusion defect before intervention and the remaining scar size measured in a second scan several days after the event.SPECT allows quantification of area at risk(AAR)and final infarct size(FIS)by tracer injection prior to revascularization and after 1 month,respectively.SPECT provides the most validated measure of myocardial salvage and has been utilized in multiple randomizedclinical trials.However,SPECT is logistically challenging,expensive,and includes radiation exposure.More recently,a large number of studies have suggested that cardiac magnetic resonance(CMR)can determine salvage in a single examination by combining measures of myocardial oedema in the AAR exposed to ischaemia reperfusion with FIS quantification by late gadolinium enhancement.
