目的:探索大鼠左冠状动脉前降支不同结扎处理后,对心肌形态学及心功能的影响,以建立适合移植干细胞再生修复心肌梗死研究的稳定、可靠和更合乎发病机理的动物模型。方法:雄性W istar大鼠70只,随机分为六组即:假手术组、结扎(15 m in、30...目的:探索大鼠左冠状动脉前降支不同结扎处理后,对心肌形态学及心功能的影响,以建立适合移植干细胞再生修复心肌梗死研究的稳定、可靠和更合乎发病机理的动物模型。方法:雄性W istar大鼠70只,随机分为六组即:假手术组、结扎(15 m in、30 m in、45 m in、60 m in)再灌、结扎非再灌。于处理后1 d、1周、2周或4周动态观察心肌梗死变化,并于处理一月后测量动脉收缩压(ASP)、动脉舒张压(ADP)、左室收缩压(LVSP)、左室舒张末压(LV-EDP)及左室压力上升及下降最大速度(±dp/dtm ax)。结果:引起明显的心肌梗死至少需要结扎30 m in。结扎(45m in、60 m in)再灌、结扎非再灌的心肌梗死明显,并观察到梗死区域心肌已绝大部分纤维化,且梗死面积变化较恒定。同时测定不同结扎时间心功能的变化发现,结扎(45 m in、60 m in)再灌或结扎非再灌各组ASP、ADP、LVSP、±dp/dtm ax显著下降,LVEDP明显升高。并且不同结扎时间处理后,大鼠心功能的变化与心肌梗死后的梗死面积变化密切相关。结论:建立了在实验大鼠左冠状动脉前降支中上1/3处结扎45 m in以上的大鼠心肌梗死模型,不仅合乎临床心肌梗死的发病机理,而且梗死部位、梗死区域面积稳定,适合于移植细胞再生修复心肌梗死的研究。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
目的应用大鼠在体心肌梗死后心室重构模型,探讨不同时间段重组人促红细胞生成素(recombinant human erythropoietin,rHu-EPO)对心肌梗死大鼠血流动力学、心功能及左室梗死面积的影响.探讨EPO抑制心肌梗死后心脏重构的给药时机和方案,为...目的应用大鼠在体心肌梗死后心室重构模型,探讨不同时间段重组人促红细胞生成素(recombinant human erythropoietin,rHu-EPO)对心肌梗死大鼠血流动力学、心功能及左室梗死面积的影响.探讨EPO抑制心肌梗死后心脏重构的给药时机和方案,为临床应用提供实验依据.方法选取健康SD大鼠60只,随机分为假手术组、单纯心肌梗死后心脏重构组、不同药物干预组(rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组)各5只.在冠状动脉前降支的上1/3点以上处穿线结扎,制作心肌梗死模型,喂养4周.不同药物干预组在缺血开始前皮下注射药物,以后每周2次.分别于术后24 h、2周、4周测定血流动力学参数,记录左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室内压最大上升速率(+dp/d)t和左室内压最大下降速率(-dp/d)t,并记录同步心率(HR).4周后处死动物收集心脏标本,根据左右心室实际重量(LVW、RVW),计算左右心室相对重量(LV/BW、RV/BW).TTC及伊文式蓝染色检测左室梗死面积、病理检测大体和镜下形态学改变.结果术后24 h:与假手术组相比,单纯心肌梗死后心脏重构组左室收缩压(LVSP)、左室舒张末期压(LVEDP)和左室内压最大上升和下降速率(±dp/d)t明显异常,LVSP、±dp/dt均显著降低,LVEDP显著升高(P<0.05);与单纯心肌梗死后心脏重构组相比,不同药物干预组(rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组)±dp/dt有明显改善(P<0.05).术后2周:与假手术组相比,单纯心肌梗死后心脏重构组LVSP、LVEDP和±dp/dt显著恶化(P<0.05);与单纯心肌梗死后心脏重构组相比,不同药物干预组(rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组)±dp/dt有显著改善(P<0.05).术后4周:与假手术组相比,单纯心肌梗死后心脏重构组LVSP、LVEDP和±dp/dt显著恶化(P<0.05);与单纯心肌梗死后心脏重构组相比,不同药物干预组(rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组)±dp/dt有显著改善(P<0展开更多
Following myocardial infarction(MI), cardiomyocytes and infarct size are the focus of our attention when evaluating the extent of cardiac injury, efficacy of therapies or success in repairing the damaged heart by stem...Following myocardial infarction(MI), cardiomyocytes and infarct size are the focus of our attention when evaluating the extent of cardiac injury, efficacy of therapies or success in repairing the damaged heart by stem cell therapy. Numerous interventions have been shown by pre-clinical studies to be effective in limiting infarct size, and yet clinical trials designed accordingly have yielded disappointing outcomes. The ultimate goal of cardiac protection is to limit the adverse cardiac remodeling. Accumulating studies have revealed that post-infarct remodeling can be attenuated without infarct size limitation. To reconcile this, one needs to appreciate the significance of various cellular and acellular myocardial components that, like cardiomyocytes, undergo significant damage and dysfunction, which impact the ultimate cardiac injury and remodelling. Microvascular injury following ischemia-reperfusion may influence infarct size and promote inflammation. Myocardial injury evokes innate immunity with massive inflammatory infiltration that, although essential for the healing process, exacerbates myocardial injury and damage to extracellular matrix leading to dilative remodeling. It is also important to consider the multiple non-cardiomyocyte components in evaluating therapeutic efficacy. Current research indicates the pivotal role of these components in achieving cardiac regeneration by cell therapy. This review summarizes findings in this field, highlights a broad consideration of therapeutic targets,and recommends cardiac remodeling as the ultimate target.展开更多
文摘目的:探索大鼠左冠状动脉前降支不同结扎处理后,对心肌形态学及心功能的影响,以建立适合移植干细胞再生修复心肌梗死研究的稳定、可靠和更合乎发病机理的动物模型。方法:雄性W istar大鼠70只,随机分为六组即:假手术组、结扎(15 m in、30 m in、45 m in、60 m in)再灌、结扎非再灌。于处理后1 d、1周、2周或4周动态观察心肌梗死变化,并于处理一月后测量动脉收缩压(ASP)、动脉舒张压(ADP)、左室收缩压(LVSP)、左室舒张末压(LV-EDP)及左室压力上升及下降最大速度(±dp/dtm ax)。结果:引起明显的心肌梗死至少需要结扎30 m in。结扎(45m in、60 m in)再灌、结扎非再灌的心肌梗死明显,并观察到梗死区域心肌已绝大部分纤维化,且梗死面积变化较恒定。同时测定不同结扎时间心功能的变化发现,结扎(45 m in、60 m in)再灌或结扎非再灌各组ASP、ADP、LVSP、±dp/dtm ax显著下降,LVEDP明显升高。并且不同结扎时间处理后,大鼠心功能的变化与心肌梗死后的梗死面积变化密切相关。结论:建立了在实验大鼠左冠状动脉前降支中上1/3处结扎45 m in以上的大鼠心肌梗死模型,不仅合乎临床心肌梗死的发病机理,而且梗死部位、梗死区域面积稳定,适合于移植细胞再生修复心肌梗死的研究。
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.
文摘目的应用大鼠在体心肌梗死后心室重构模型,探讨不同时间段重组人促红细胞生成素(recombinant human erythropoietin,rHu-EPO)对心肌梗死大鼠血流动力学、心功能及左室梗死面积的影响.探讨EPO抑制心肌梗死后心脏重构的给药时机和方案,为临床应用提供实验依据.方法选取健康SD大鼠60只,随机分为假手术组、单纯心肌梗死后心脏重构组、不同药物干预组(rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组)各5只.在冠状动脉前降支的上1/3点以上处穿线结扎,制作心肌梗死模型,喂养4周.不同药物干预组在缺血开始前皮下注射药物,以后每周2次.分别于术后24 h、2周、4周测定血流动力学参数,记录左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室内压最大上升速率(+dp/d)t和左室内压最大下降速率(-dp/d)t,并记录同步心率(HR).4周后处死动物收集心脏标本,根据左右心室实际重量(LVW、RVW),计算左右心室相对重量(LV/BW、RV/BW).TTC及伊文式蓝染色检测左室梗死面积、病理检测大体和镜下形态学改变.结果术后24 h:与假手术组相比,单纯心肌梗死后心脏重构组左室收缩压(LVSP)、左室舒张末期压(LVEDP)和左室内压最大上升和下降速率(±dp/d)t明显异常,LVSP、±dp/dt均显著降低,LVEDP显著升高(P<0.05);与单纯心肌梗死后心脏重构组相比,不同药物干预组(rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组)±dp/dt有明显改善(P<0.05).术后2周:与假手术组相比,单纯心肌梗死后心脏重构组LVSP、LVEDP和±dp/dt显著恶化(P<0.05);与单纯心肌梗死后心脏重构组相比,不同药物干预组(rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组)±dp/dt有显著改善(P<0.05).术后4周:与假手术组相比,单纯心肌梗死后心脏重构组LVSP、LVEDP和±dp/dt显著恶化(P<0.05);与单纯心肌梗死后心脏重构组相比,不同药物干预组(rHu-EPO干预组、SB203580组、rHu-EPO+SB203580组)±dp/dt有显著改善(P<0
基金supported by the National Health and Medical Research Council of Australia fellowship(ID1043026 to Xiaojun Du)
文摘Following myocardial infarction(MI), cardiomyocytes and infarct size are the focus of our attention when evaluating the extent of cardiac injury, efficacy of therapies or success in repairing the damaged heart by stem cell therapy. Numerous interventions have been shown by pre-clinical studies to be effective in limiting infarct size, and yet clinical trials designed accordingly have yielded disappointing outcomes. The ultimate goal of cardiac protection is to limit the adverse cardiac remodeling. Accumulating studies have revealed that post-infarct remodeling can be attenuated without infarct size limitation. To reconcile this, one needs to appreciate the significance of various cellular and acellular myocardial components that, like cardiomyocytes, undergo significant damage and dysfunction, which impact the ultimate cardiac injury and remodelling. Microvascular injury following ischemia-reperfusion may influence infarct size and promote inflammation. Myocardial injury evokes innate immunity with massive inflammatory infiltration that, although essential for the healing process, exacerbates myocardial injury and damage to extracellular matrix leading to dilative remodeling. It is also important to consider the multiple non-cardiomyocyte components in evaluating therapeutic efficacy. Current research indicates the pivotal role of these components in achieving cardiac regeneration by cell therapy. This review summarizes findings in this field, highlights a broad consideration of therapeutic targets,and recommends cardiac remodeling as the ultimate target.
