喷射心肌打孔填充凝胶支架治疗犬心肌梗死
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摘要
背景和目的:
心肌打孔术(TMR)即利用激光或者机械方式在心脏缺血区制作多个与左心室腔相通的孔道,使心腔内血液注入到缺血心肌内,同时通过血管新生可以营养该区域心肌,从而改善缺血心肌灌注。激光心肌打孔术(TMLR)作为治疗顽固性心绞痛和晚期缺血性心脏病的一种辅助治疗方法,可以改善心绞痛症状,提高运动耐量,改善心肌灌注等,但是激光心肌孔道的闭塞以及激光对周围心肌组织的热损伤等限制了其应用。而针刺打孔和电钻打孔的心室壁孔道也同样面临心肌孔道闭塞的问题。
针对上述血运重建方法的不足,本实验采用一种新型的心肌打孔方式-喷射心肌打孔(TMJR)。该方法可以避免激光心肌打孔对心肌组织带来的热损伤,以及避免针刺打孔和电钻打孔将直硬刚针插入搏动的心脏,而且在喷射心肌打孔的同时可以喷入具有三维支架作用的凝胶,凝胶在一定时间内可以对心肌孔道起到支撑作用,从而可能使心肌孔道得以保留,而且可能使心肌孔道壁内皮化及血管化。本实验观察了正常犬喷射心肌打孔填充不同凝胶支架后心肌孔道的演变规律,以及不同凝胶支架的组织相容性;观察了在急性心肌梗死犬模型的心肌缺血梗死区行喷射心肌打孔填充凝胶支架,对心肌孔道的开放性、心肌血管新生、心室重构、以及血流动力学等影响。
方法:
1、正常活体犬喷射不同凝胶心肌打孔
犬12只,随机均分为3组(n=4):①琼脂糖凝胶组(AH组),
②纤维蛋白凝胶组(FG组),③壳聚糖凝胶组(CH组)。在各组用无针注射器分别喷射各种凝胶心肌打孔。3组均于术后2、4、6周取含有孔道的心肌组织行HE染色和Masson染色,观察
①各种凝胶支架在心肌组织中的降解性和组织相容性;②各组心肌孔道是否保留和开放;③各组心肌孔道内及孔道周围的纤维组织增生情况。
2、心肌梗死犬喷射壳聚糖凝胶心肌打孔
32只犬随机均分为4组(n=8):单纯心肌梗死组(MI组)、生理盐水组(NS组)、壳聚糖凝胶组(CH组)、壳聚糖凝胶+血管生长因子组(CH+GF组)。
MI组仅建立心肌梗死模型。NS组,CH组和CH+GF组建立心肌梗死模型后在心肌缺血梗死区用无针注射器进行喷射心肌打孔;NS组心肌孔道内喷射生理盐水,CH组喷射壳聚糖凝胶,CH+GF组喷射包载有生长因子(血管内皮生长因子联合碱性成纤维细胞生长因子)的壳聚糖凝胶。
术后6周①测量血流动力学参数;②苏木素-伊红(HE)染色和免疫组化染色观察心肌孔道的开放性以及心肌孔道的内皮化情况;③Masson染色观察心肌孔道内及孔道周围的胶原增生情况;④免疫组化染色观察缺血心肌中血管性血友病因子(VWF)、α-平滑肌肌动蛋白(a-SMA)的表达,计算微血管、小血管以及小动脉的密度;⑤计算心肌梗死面积、左右心室重量指数;⑥计算心肌组织中Ⅰ、Ⅲ型胶原容积分数及Ⅰ/Ⅲ比值。
结果:
1、正常活体犬喷射不同凝胶心肌打孔
①琼脂糖凝胶的生物降解性和组织相容性差,引起周围组织大量胶原增生,心肌孔道完全闭塞。
②纤维蛋白凝胶具有良好的生物降解性和组织相容性,但支撑度弱,其降解后心肌孔道基本闭塞。
③壳聚糖凝胶具有良好的生物降解性、组织相容性及良好的支撑度,其降解后可见心肌孔道开放及心肌孔道壁内皮化,心肌孔道内及孔道周围少量纤维组织增生。
2、心肌梗死犬喷射壳聚糖凝胶心肌打孔
①术后6周,HE染色和免疫组化染色示:NS组心肌孔道基本闭塞,CH组和CH+GF组均可见孔道开放,而CH+GF组孔道壁内皮化更明显。
②Masson染色示:NS组心肌孔道内有大量的胶原纤维填充,CH组和CH+GF组的心肌孔道有部分胶原纤维,尚有大量空腔存在。
③和MI组比较,NS组、CH组和CH+GF组的小血管显著增加(P<0.05);和NS组比较,CH组和CH+GF组的小血管显著增多(P<0.05),以CH+GF组更显著;而CH+GF组的小动脉较MI组和NS组均显著增多(P<0.05)。
④和MI组比较,CH组的Ⅰ型胶原容积分数显著减少(P<0.05);和MI组、NS组及CH组比较,CH+GF组的Ⅲ型胶原容积分数显著增加(P<0.05);和MI组、NS组比较,CH组及CH+GF组的Ⅰ/Ⅲ比值均显著减少(P<0.05)。
⑤CH组和CH+GF组的部分血流动力学参数较MI组显著改善(P<0.05)。
结论:
1、喷射心肌打孔填充凝胶支架具有可行性;
2、琼脂糖凝胶和纤维蛋白凝胶均不适合作为心肌打孔的孔道填充物,而喷射壳聚糖凝胶心肌打孔能使心肌孔道开放;
3、喷射心肌打孔填充壳聚糖凝胶支架可使心肌梗死犬的心肌孔道开放和孔道壁内皮化、促进血管新生,改善心室重构,有利于血流动力学功能的改善。
Background and Objective:Transmyocardial revascularization(TMR) is a process in which channels are created into ischemic myocardium by either laser or mechanical means to enhance myocardial perfusion by directly supplying tissue with endoventricular oxygenated blood or angiogenesis. Transmyocardial laser revascularization(TMLR) is a supplementary treatment for patients with refractory angina pectoris and severe end-stage coronary artery disease who are not amenable to conventional revascularization. TMLR could improve the symptoms of angina, exercise tolerance, myocardial perfusion and function. However, disadvantages such as the occlusion of laser transmyocardial channels and the heat injury to surrounding myocardium limited its application. Similarly, the channels made by needles or drills were occluded too.
Therefore we devised a new treatment strategy-transmyocardial jet revascularization (TMJR) . This new method could avoid laser caused heat injury during TMLR and avoid injury of needles or drills inserting the beating heart during TMR with needles or drills. And at the same time of TMJR, the hydrogel scaffold could been delivered into the channels made by TMJR. The hydrogel scaffold in channels could support the channels for a time and the channels may be retained, endothelialization and vascularization. Therefore, we investigated the transmyocardial channels changes after TMJR with different hydrogel scaffolds filling the channels and histocompatibility of different hydrogel scaffolds in canine nomal myocardium; And we investigated the effect of TMJR with hydrogel scaffold on transmyocardial channel patency , myocardial angiogenesis, ventricular remodeling and hemodynamic function after MI in a canine model.
Methods:
1. Transmyocardial jet revascularization with different hydrogel scaffolds filling the channels in canine nomal hearts
Twelve canines were randomly divided into three groups(n=4):①Agarose hydrogel group (AH group);②Fibrin glue group (GF group);③Chitosan hydrogel group (CH group).
Transmyocardial revascularization in different groups was performed with needle-free systems jeting out different hydrogels. Myocadium including channels in three groups were obtained at 2,4,6 weeks for hematoxylin-eosin (HE) staining and Masson's trichrome staining to observe①the degradation and histocompatibility of the three hydrogels in myocardium;②whether the channels in three groups could keep patency;③fibrosis inside and around the transmyocardial channels in three groups.
2. Transmyocardial jet revascularization with chitosan hydrogel filling the channels in canine infarcted hearts
32 canines were randomly divided into four groups(n=8): myocardial infarction group(MI group), nomal saline group (NS group), chitosan hydrogel group (CH group), and chitosan incorporating grow factors group(CH+GF group).
Myocardial infarction was induced in canines by ligating the left anterior descending coronary artery. In MI group, myocardial infarction was made. And in NS group, CH group and CH+GF group, transmyocardial revascularization was performed at the ischemia and infarcted myocardium after myocardial infarction with needle-free systems. The transmyocardial channels in NS group were filled with nomal saline, the channels in CH group with chitosan, and the channels in CH+GF group with Chitosan incorporating vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).
After 6 weeks, the animals underwent hemodynamic analysis. The patency of channels and the endothelialization of channels were observed from hematoxylin-eosin (HE) staining and immunohistochemistry. Fibrosis inside and around the transmyocardial channels was assessed by Masson's trichrome staining. The expression of von Willebrand factor(VWF ) and a-smooth muscle actin (a-SMA) in ischemic myocardium were detected by immunohistochemistry and the density of microvascular , small blood vessels and arterioles were messured. The infarct size, the left and right ventricular weight index were recorded. In addition, the collagen volume fraction of type-Ⅰand type-Ⅲcollagen and theⅠ/Ⅲratio in myocardium were recorded.
Results:
1. Transmyocardial jet revascularization with different hydrogel scaffolds filling the channels in canine nomal hearts
①Agarose hydrogel had bad biodegradation and histocompatibility, making the collagen fibers proliferation of the surrounding tissue and making the channels occluded.
②Fibrin glue had good biodegradation and histocompatibility,while the mechanical strength was weak and the channels were almost occluded after the degradation of fibrin glue.
③Chitosan hydrogel had excellent biodegradation, histocompatibility and mechanical strength. The channels were open and endothelialization after it degraded. Little fibrosis inside and around the transmyocardial channels was observed.
2. Transmyocardial jet revascularization with chitosan hydrogel filling the channels in canine infarcted hearts
①After 6 weeks of TMJR, HE staining and immunohistochemistry showed that the channels in NS group were occluded and the channels in CH group and CH+GF group could keep patency. Luminal endothelization was more obvious in CH+GF group.
②Masson's trichrome staining showed thar the channels in NS group were filled with collagen fibers. However in CH and CH+GF group, the channels were open with less collagen fibers.
③The small blood vessels in NS group, CH group and CH+GF group increased significantly compared with the MI group (P<0.05); the small blood vessels in CH group and CH+GF group increased significantly compared with the NS group (P<0.05),especially in CH+GF group; the arterioles in CH+GF group increased significantly compared with the MI group and NS group (P<0.05).
④Compared with MI group, the collagen volume of type-Ⅰcollagen in CH group decreased significantly(P<0.05); the collagen volume of type-Ⅲcollagen in CH+GF group increased significantly Compared with MI group, NS group and CH group (P<0.05). And theⅠ/Ⅲratio in CH group and CH+GF group were lower than MI group and NS group (P<0.05).
⑤Some of the hemodynamic parameters in CH group and CH+GF group were significantly improved compared with MI group(P<0.05).
Conclusions:
1. Transmyocardial jet revascularization with different hydrogel scaffolds filling the channels is feasible;
2. Agarose hydrogel and fibrin glue are not suitable as a channels filler of transmyocardial revascularization. However TMJR with the chitosan hydrogel filling the channels could keep the channels patency.
3. TMJR with the chitosan hydrogel filling the channels could keep the channels patency and endothelialization in canine infarcted hearts, enhance angiogenesis, improve ventricular remodeling and hemodynamic function.
心肌打孔术(TMR)即利用激光或者机械方式在心脏缺血区制作多个与左心室腔相通的孔道,使心腔内血液注入到缺血心肌内,同时通过血管新生可以营养该区域心肌,从而改善缺血心肌灌注。激光心肌打孔术(TMLR)作为治疗顽固性心绞痛和晚期缺血性心脏病的一种辅助治疗方法,可以改善心绞痛症状,提高运动耐量,改善心肌灌注等,但是激光心肌孔道的闭塞以及激光对周围心肌组织的热损伤等限制了其应用。而针刺打孔和电钻打孔的心室壁孔道也同样面临心肌孔道闭塞的问题。
针对上述血运重建方法的不足,本实验采用一种新型的心肌打孔方式-喷射心肌打孔(TMJR)。该方法可以避免激光心肌打孔对心肌组织带来的热损伤,以及避免针刺打孔和电钻打孔将直硬刚针插入搏动的心脏,而且在喷射心肌打孔的同时可以喷入具有三维支架作用的凝胶,凝胶在一定时间内可以对心肌孔道起到支撑作用,从而可能使心肌孔道得以保留,而且可能使心肌孔道壁内皮化及血管化。本实验观察了正常犬喷射心肌打孔填充不同凝胶支架后心肌孔道的演变规律,以及不同凝胶支架的组织相容性;观察了在急性心肌梗死犬模型的心肌缺血梗死区行喷射心肌打孔填充凝胶支架,对心肌孔道的开放性、心肌血管新生、心室重构、以及血流动力学等影响。
方法:
1、正常活体犬喷射不同凝胶心肌打孔
犬12只,随机均分为3组(n=4):①琼脂糖凝胶组(AH组),
②纤维蛋白凝胶组(FG组),③壳聚糖凝胶组(CH组)。在各组用无针注射器分别喷射各种凝胶心肌打孔。3组均于术后2、4、6周取含有孔道的心肌组织行HE染色和Masson染色,观察
①各种凝胶支架在心肌组织中的降解性和组织相容性;②各组心肌孔道是否保留和开放;③各组心肌孔道内及孔道周围的纤维组织增生情况。
2、心肌梗死犬喷射壳聚糖凝胶心肌打孔
32只犬随机均分为4组(n=8):单纯心肌梗死组(MI组)、生理盐水组(NS组)、壳聚糖凝胶组(CH组)、壳聚糖凝胶+血管生长因子组(CH+GF组)。
MI组仅建立心肌梗死模型。NS组,CH组和CH+GF组建立心肌梗死模型后在心肌缺血梗死区用无针注射器进行喷射心肌打孔;NS组心肌孔道内喷射生理盐水,CH组喷射壳聚糖凝胶,CH+GF组喷射包载有生长因子(血管内皮生长因子联合碱性成纤维细胞生长因子)的壳聚糖凝胶。
术后6周①测量血流动力学参数;②苏木素-伊红(HE)染色和免疫组化染色观察心肌孔道的开放性以及心肌孔道的内皮化情况;③Masson染色观察心肌孔道内及孔道周围的胶原增生情况;④免疫组化染色观察缺血心肌中血管性血友病因子(VWF)、α-平滑肌肌动蛋白(a-SMA)的表达,计算微血管、小血管以及小动脉的密度;⑤计算心肌梗死面积、左右心室重量指数;⑥计算心肌组织中Ⅰ、Ⅲ型胶原容积分数及Ⅰ/Ⅲ比值。
结果:
1、正常活体犬喷射不同凝胶心肌打孔
①琼脂糖凝胶的生物降解性和组织相容性差,引起周围组织大量胶原增生,心肌孔道完全闭塞。
②纤维蛋白凝胶具有良好的生物降解性和组织相容性,但支撑度弱,其降解后心肌孔道基本闭塞。
③壳聚糖凝胶具有良好的生物降解性、组织相容性及良好的支撑度,其降解后可见心肌孔道开放及心肌孔道壁内皮化,心肌孔道内及孔道周围少量纤维组织增生。
2、心肌梗死犬喷射壳聚糖凝胶心肌打孔
①术后6周,HE染色和免疫组化染色示:NS组心肌孔道基本闭塞,CH组和CH+GF组均可见孔道开放,而CH+GF组孔道壁内皮化更明显。
②Masson染色示:NS组心肌孔道内有大量的胶原纤维填充,CH组和CH+GF组的心肌孔道有部分胶原纤维,尚有大量空腔存在。
③和MI组比较,NS组、CH组和CH+GF组的小血管显著增加(P<0.05);和NS组比较,CH组和CH+GF组的小血管显著增多(P<0.05),以CH+GF组更显著;而CH+GF组的小动脉较MI组和NS组均显著增多(P<0.05)。
④和MI组比较,CH组的Ⅰ型胶原容积分数显著减少(P<0.05);和MI组、NS组及CH组比较,CH+GF组的Ⅲ型胶原容积分数显著增加(P<0.05);和MI组、NS组比较,CH组及CH+GF组的Ⅰ/Ⅲ比值均显著减少(P<0.05)。
⑤CH组和CH+GF组的部分血流动力学参数较MI组显著改善(P<0.05)。
结论:
1、喷射心肌打孔填充凝胶支架具有可行性;
2、琼脂糖凝胶和纤维蛋白凝胶均不适合作为心肌打孔的孔道填充物,而喷射壳聚糖凝胶心肌打孔能使心肌孔道开放;
3、喷射心肌打孔填充壳聚糖凝胶支架可使心肌梗死犬的心肌孔道开放和孔道壁内皮化、促进血管新生,改善心室重构,有利于血流动力学功能的改善。
Background and Objective:Transmyocardial revascularization(TMR) is a process in which channels are created into ischemic myocardium by either laser or mechanical means to enhance myocardial perfusion by directly supplying tissue with endoventricular oxygenated blood or angiogenesis. Transmyocardial laser revascularization(TMLR) is a supplementary treatment for patients with refractory angina pectoris and severe end-stage coronary artery disease who are not amenable to conventional revascularization. TMLR could improve the symptoms of angina, exercise tolerance, myocardial perfusion and function. However, disadvantages such as the occlusion of laser transmyocardial channels and the heat injury to surrounding myocardium limited its application. Similarly, the channels made by needles or drills were occluded too.
Therefore we devised a new treatment strategy-transmyocardial jet revascularization (TMJR) . This new method could avoid laser caused heat injury during TMLR and avoid injury of needles or drills inserting the beating heart during TMR with needles or drills. And at the same time of TMJR, the hydrogel scaffold could been delivered into the channels made by TMJR. The hydrogel scaffold in channels could support the channels for a time and the channels may be retained, endothelialization and vascularization. Therefore, we investigated the transmyocardial channels changes after TMJR with different hydrogel scaffolds filling the channels and histocompatibility of different hydrogel scaffolds in canine nomal myocardium; And we investigated the effect of TMJR with hydrogel scaffold on transmyocardial channel patency , myocardial angiogenesis, ventricular remodeling and hemodynamic function after MI in a canine model.
Methods:
1. Transmyocardial jet revascularization with different hydrogel scaffolds filling the channels in canine nomal hearts
Twelve canines were randomly divided into three groups(n=4):①Agarose hydrogel group (AH group);②Fibrin glue group (GF group);③Chitosan hydrogel group (CH group).
Transmyocardial revascularization in different groups was performed with needle-free systems jeting out different hydrogels. Myocadium including channels in three groups were obtained at 2,4,6 weeks for hematoxylin-eosin (HE) staining and Masson's trichrome staining to observe①the degradation and histocompatibility of the three hydrogels in myocardium;②whether the channels in three groups could keep patency;③fibrosis inside and around the transmyocardial channels in three groups.
2. Transmyocardial jet revascularization with chitosan hydrogel filling the channels in canine infarcted hearts
32 canines were randomly divided into four groups(n=8): myocardial infarction group(MI group), nomal saline group (NS group), chitosan hydrogel group (CH group), and chitosan incorporating grow factors group(CH+GF group).
Myocardial infarction was induced in canines by ligating the left anterior descending coronary artery. In MI group, myocardial infarction was made. And in NS group, CH group and CH+GF group, transmyocardial revascularization was performed at the ischemia and infarcted myocardium after myocardial infarction with needle-free systems. The transmyocardial channels in NS group were filled with nomal saline, the channels in CH group with chitosan, and the channels in CH+GF group with Chitosan incorporating vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).
After 6 weeks, the animals underwent hemodynamic analysis. The patency of channels and the endothelialization of channels were observed from hematoxylin-eosin (HE) staining and immunohistochemistry. Fibrosis inside and around the transmyocardial channels was assessed by Masson's trichrome staining. The expression of von Willebrand factor(VWF ) and a-smooth muscle actin (a-SMA) in ischemic myocardium were detected by immunohistochemistry and the density of microvascular , small blood vessels and arterioles were messured. The infarct size, the left and right ventricular weight index were recorded. In addition, the collagen volume fraction of type-Ⅰand type-Ⅲcollagen and theⅠ/Ⅲratio in myocardium were recorded.
Results:
1. Transmyocardial jet revascularization with different hydrogel scaffolds filling the channels in canine nomal hearts
①Agarose hydrogel had bad biodegradation and histocompatibility, making the collagen fibers proliferation of the surrounding tissue and making the channels occluded.
②Fibrin glue had good biodegradation and histocompatibility,while the mechanical strength was weak and the channels were almost occluded after the degradation of fibrin glue.
③Chitosan hydrogel had excellent biodegradation, histocompatibility and mechanical strength. The channels were open and endothelialization after it degraded. Little fibrosis inside and around the transmyocardial channels was observed.
2. Transmyocardial jet revascularization with chitosan hydrogel filling the channels in canine infarcted hearts
①After 6 weeks of TMJR, HE staining and immunohistochemistry showed that the channels in NS group were occluded and the channels in CH group and CH+GF group could keep patency. Luminal endothelization was more obvious in CH+GF group.
②Masson's trichrome staining showed thar the channels in NS group were filled with collagen fibers. However in CH and CH+GF group, the channels were open with less collagen fibers.
③The small blood vessels in NS group, CH group and CH+GF group increased significantly compared with the MI group (P<0.05); the small blood vessels in CH group and CH+GF group increased significantly compared with the NS group (P<0.05),especially in CH+GF group; the arterioles in CH+GF group increased significantly compared with the MI group and NS group (P<0.05).
④Compared with MI group, the collagen volume of type-Ⅰcollagen in CH group decreased significantly(P<0.05); the collagen volume of type-Ⅲcollagen in CH+GF group increased significantly Compared with MI group, NS group and CH group (P<0.05). And theⅠ/Ⅲratio in CH group and CH+GF group were lower than MI group and NS group (P<0.05).
⑤Some of the hemodynamic parameters in CH group and CH+GF group were significantly improved compared with MI group(P<0.05).
Conclusions:
1. Transmyocardial jet revascularization with different hydrogel scaffolds filling the channels is feasible;
2. Agarose hydrogel and fibrin glue are not suitable as a channels filler of transmyocardial revascularization. However TMJR with the chitosan hydrogel filling the channels could keep the channels patency.
3. TMJR with the chitosan hydrogel filling the channels could keep the channels patency and endothelialization in canine infarcted hearts, enhance angiogenesis, improve ventricular remodeling and hemodynamic function.
引文
[1] Wearn JT, Mettier SR , Klump TG, et al. The nature of the vascular communication between the coronary arteries and the chambers of the heart [J]. Am Heart J. 1933, 9: 143-164.
[2] Gassler N, Stubbe HM. Clinical data and histological features of transmyocardial revascularization with CO2-laser [J]. Eur J Cardiothorac Surg. 1997, 12(1): 25-30.
[3] Mueller XM, Tevaearai HT, Chaubert P, et al. Does laser injury induce a different neovascularisation pattern from mechanical or ischaemic injuries [J]? Heart. 2001, 85(6): 697-701.
[4] Huikeshoven M, Beli?n JA, Tukkie R, et al. The vascular response induced by transmyocardial laser revascularization is determined by the size of the channel scar: Results of CO2, holmium and excimer lasers [J]. Lasers Surg Med. 2004, 35(1): 35-40.
[5] Tasse J, Arora R. Transmyocardial revascularization: peril and potential[J]. J Cardiovasc Pharmacol Ther. 2007, 12(1): 44-53.
[6] Briones E, Lacalle JR, Marin I. Transmyocardial laser revascularization versus medical therapy for refractory angina [J]. Cochrane Database Syst Rev. 2009, 21 (1): CD003712.
[7] Chu VF, Giaid A, Kuang JQ, et a1. Thoracic Surgery Directors Association Award. Angiogenesis in transmyocardial revascularization: comparison of laser versus mechanical punctures [J]. Ann Thorae Surg. 1999, 68(2):301-307.
[8] Mack CA, Magovern CJ,Hahn RT,et al. Channel patency and neovascularization after transmyocardial revascularlzation using an excimer laser, results and comparisons to nonlased channels [J]. Circulation. 1997, 96(9): II65- II69.
[9] Whittaker P. Transmyocardial revascularization: the fate of myocardial channels [J]. Ann Thorac Surg. 1999, 68(6): 2376-2382.
[10] Arora A, Hakim I, Baxter J,et al. Needle-free delivery of macromolecules across the skin by nanoliter-volume pulsed microjets [J]. Proc Natl Acad Sci U S A. 2007, 104(11): 4255-4260.
[11]吴俊,孙俊英.软骨组织工程支架材料研究进展[J].中国矫形外科杂志. 2004, 12(3,4): 282-284.
[12] Wagner S, Dues G, Sawitzky D,et al. Assessment of the biological performance of the needle-free injector INJEX using the isolated porcine forelimb[J]. Br J Dermatol. 2004, 150(3): 455–461.
[13] Normand V, Lootens DL, Amici E. New insight into agarose gel mechanical properties[J]. Biomacromolecules. 2000, 1(4), 730-738.
[14] Figge FH,Barnett DJ. Anatomic evaluation of a jet injection instrument designed to minimize pain and inconvenience of parenteral therapy[J]. Am Pract Dig Treat. 1948, 3 (4): 197– 206.
[15] Perkin FS. Jet injection of insulin in treatment of diabetes mellitus[J]. Proc Am Diabetes Assoc. 1950, 10: 185–199.
[16] Hingson RA, Davis HS, Rosen M. Historical development of jet injection and envisioned uses in mass immunization and mass therapy based upon 2 decades experience[J]. Mil Med. 1963,128(6): 516.
[17] Choi AH, Smiley K, Basu M, et al. Protection of mice against rotavirus challenge following intradermal DNA immunization by Biojector needle-free injection[J]. Vaccine , 2007, 25 (16):3215-3218.
[18] Baxter J, Mitragotri S. Needle-free liquid jet injections: mechanisms and applications[J]. Expert Rev Med Devices. 2006, 3 (5): 565-574.
[19] Benedek K, Walker E, Doshier LA, et al. Studies on the use of needle-free injection device on proteins[J]. J Chromatogr A, 2005, 1079 (1-2): 397-407.
[20] Schramm-Baxter J, Mitragotri S. Needle-free jet injections: dependence of jet penetration and dispersion in the skin on jet power[J]. J Control Release. 2004, 97(3): 527-535.
[21]石卫东,刘美含,李新颖等.定量组织速度成像及组织追踪成像技术与MRI检查评价急性心肌梗死犬左室壁节段性运动异常的对照研究[J].吉林医学,2009,30(19):2235-2239.
[22] Modersohn D, Eddicks S, Ast I, et al. Influence of transmyocardial laser revascularization (TMLR) on regional cardiac function and metabolism in an isolated hemoperfused working pig heart[J]. Int J Artif Organs, 2002, 25( 11): 1074-1081.
[23] Lu WN, LüSH, Wang HB, et a1. Functional improvement of infarcted heart by co-Injection of embryonic stem cells with temperature-responsive chitosan hydrogel[J]. Tissue Eng Part A. 2009, 15(6): 1437-1447.
[24] Allen KB, Kelly J, Borkon AM, et a1. Transmyocardial laser revascularization: from randomized trials to clinical practice. A review of techniques, evidence-based outcomes, and future directions[J]. Anesthesiol Clin, 2008, 26(3): 501-519.
[25] Cooley DA, Frazier OH, Kadipasaoglu KA, et a1. Transmyocardial laser revascu- larization:anatomic evidence of long-term channel potency[J ]. Texas Heart Inst J. 1994, 21(3): 220-224.
[26] Domkowski PW, Biswas SS, Steenbergen C, et a1. Histological evidence of anglogenesis 9 months after transmyocardial laser revascularization[J]. Circulation. 2001, 103(3): 469-471.
[27]李长青,周跃.椎间盘组织工程支架材料研究进展[J].中国修复重建外科杂志, 2005, 19(12): 1033-1035.
[28]王伟,范明,智小东等.神经支架复合体修复周围神经缺损[J].中国医学科学院学报, 2005, 279(6): 688-669.
[29] Bensaid W, Triffitt JT, Blanchat C, et al. A biodegradable fibrin scaffold for mesenchymal stem cell transplantation[J]. Biomaterials. 2003, 24(14): 2497-2502.
[30] Yu J, Christman KL, Chin E, et al. Restoration of left ventricular geometry and improvement of left ventricular function in a rodent model of chronic ischemic cardiomyopathy[J]. J Thorac Cardiovasc Surg. 2009, 137(1): 180-187.
[31] Mukherjee R, Zavadzkas JA, Saunders SM, et al. Targeted myocardial microinjections of a biocomposite material reduces infarct expansion in pigs[J].Ann Thorac Surg. 2008, 86(4): 1268-1276.
[32]朱向明,王新房,刘望彭,等.激光心肌打孔隧道埋植bFGF缓释胶对急性缺血心肌血管生成及血流灌注的影响[J].中国超声医学杂志, 2004, 20(1): 4-8.
[33] Jiang T, Kumbar SG, Nair LS, et al. Biologically active chitosan systems for tissue engineering and regenerative medicine[J]. Curr Top Med Chem. 2008, 8(4): 354-364.
[34] Kang GD, Song SC. Effect of chitosan on the release of protein from thermosensitive poly(organophosphazene) hydrogels[J]. Int J Pharm. 2008, 349(1-2): 188-195.
[35] Xia P, Hou C, Wang W. Inhibitive effects of chitosan on proliferation of fibroblasts in vitro[J]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2007, 21(8): 833-836.
[36] Molinaro G, Leroux JC, Damas J, et al. Biocompatibility of thermosensitive chitosan-based hydrogels: an in vivo experimental approach to injectable biomaterials[J]. Biomaterials. 2002 , 23(13): 2717-2722.
[37] Mori T, Okumura M, Matsuura M, et al. Effects of chintin and its derivatives on the proliferation and cytokine production of fibroblasts in vivo[J]. Biomaterials. 1997 , 18(13): 947-951.
[38] Ahmed TA, Dare EV, Hincke M. Fibrin: A Versatile Scaffold for Tissue Engineering Applications[J]. Tissue Eng PartB Rev. 2008 May 1.
[39]朱爱萍,吴钧,张娜等.壳聚糖-一种具有应用潜力的组织工程支架材料.化学通报, 2002, 65(3): 1-5.
[40] Zardini P. Left ventricular remodeling after myocardial infarction [J]. Cardiologia. 1995, 40(11): 801-802.
[41] Simons M, Annex BH, Laham RJ, et al. Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: double-blind, randomized, controlled clinical trial[J] . Circulation. 2002 , 105(7): 788-793.
[42] Yl?-Herttuala S, Rissanen TT, Vajanto I, et al. Vascular endothelial growth factors: biology and current status of clinical applications in cardiovascular medicine[J]. J Am Coll Cardiol. 2007, 49(10): 1015-1026.
[43] Kim IY, Seo SJ, Moon HS, et al. Chitosan and its derivatives for tissueengineering applications[J]. Biotechnol Adv, 2008, 26(1): 1-21.
[44] Nguyen MK, Lee DS. Injectable Biodegradable Hydrogels[J]. Macromol Biosci. 2010 Mar 1.
[45] Desai PN, Yuan Q, Yang H. Synthesis and characterization of photocurable polyamidoamine dendrimer hydrogels as a versatile platform for tissue engineering and drug delivery[J]. Biomacromolecules. 2010, 11(3): 666-673.
[46] de Veies C , Escobedo JA ,Ueno H , et al. The fms - like tyrosine kinase , a receptor for vascular endothelial growth factor[J]. Science. 1992, 255(5047): 989-991.
[47] Yu PJ, Ferrari G, Galloway AC, et al. Basic fibroblast growth factor (FGF-2): the high molecular weight forms come of age[J]. J Cell Biochem. 2007,100(5): 1100-1108.
[48] Detillieux KA, Sheikh F, Kardami E ,et al. Biological activities of fibroblast growth factor-2 in the adult myocardium[J]. Cardiovasc Res. 2003 , 57(1): 8-19.
[49] Shao ZQ, Takaji K, Katayama Y, et al. Effects of intramyocardial administration of slow-release basic fibroblast growth factor on angiogenesis and ventricular remodeling in a rat infarct model[J]. Circ J. 2006 , 70(4): 471-477.
[50] Boodhwani M, Sodha NR, Laham RJ, et al. The future of therapeutic myocardial angiogenesis[J]. Shock. 2006 , 26(4): 332-341.
[51] Kano MR, Morishita Y, Iwata C, et al. VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B-PDGFRbeta signaling[J]. J Cell Sci. 2005, 118(16): 3759-3768.
[52]温铭杰,刘冰,孙丽翠等.人VEGF165和bFGF基因联合治疗大鼠急性心肌梗死.首都医科大学学报[J]. 2006, 27(5): 627-630.
[53] Yau TM, Kim C, Li G, et al. Enhanced angiogenesis with multimodal cell-based gene therapy[J]. Ann Thorac Surg. 2007, 83(3): 1110-1119.
[54] Layman H, Sacasa M, Murphy AE,et al. Co-delivery of FGF-2 and G-CSF from gelatin-based hydrogels as angiogenic therapy in a murine critical limb ischemic model[J]. Acta Biomater. 2009, 5(1): 230-239.
[55] Lu H, Xu X, Zhang M,et al. Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs[J]. Proc Natl Acad Sci U S A. 2007, 104(29): 12140-12145.
[56] Allen KB, DoMing RD, Angell ww, et a1. Transmyocardial revaseulafization: 5-year follow-up of a prospective, randomized multicenter trial[J]. Ann Thorac Snrg. 2004, 77(4): 1228-1234.
[57] Mueller XM, Tevaearai HT, Genton CY, et a1. Improved neoangiogenesis in transmyocardial laser revascularization combined with adjunct in a pig model [J]. Clin Sci(Lond). 2000, 99(6): 535-540.
[58] Tokura S, Tamura H, Azuma I. Immunological aspects of chitin and chitin derivatives administered to animals[J]. Exs .1999; 87: 279–292.
[59] Ishihara M, Obara K, Ishizuka T, et al . Controlled release of fibroblast growth factors and heparin from photocrosslinked chitosan hydrogels and subsequent effect on in vivo vascularization[J]. J Biomed Mater Res A . 2003, 64(3): 551-559.
[60] Cherian SM, Bobryshev YV, Tran D, et al. Cellular destruction following transmyocardial laser revascularization (TMR) [J]. J Mol Histol. 2005, 36(4) : 275-280.
[61] Chupa JM, Foster AM, Sumner SR, et al. Vascular cell responses to polysaccharide materials: in vitro and in vivo evaluations[J]. Biomaterials. 2000, 21(22): 2315-2322.
[62] Nakamura S, Nambu M, Ishizuka T, et al. Effect of controlled release of fibroblast growth factor-2 from chitosan/fucoidan micro complex-hydrogel on in vitro and in vivo vascularization[J]. J Biomed Mater Res A. 2008,85(3): 619-627.
[63] Yamamoto N, Kohmoto T, Roethy W, et a1. Histologic evidence that basic fibroblast growth factor enhances the angiogenic effects of transmyocardial laser revascularization [J]. Basic Res Cardiol. 2000, 95(1): 55-63.
[64]朱向明,王新房,刘望彭等.激光心肌打孔隧道埋植bFGF缓释胶对急性缺血心肌血管生成及血流灌注的影响[J].中国超声医学杂志. 2004, 20(1): 4-8.
[65] Liu XC, Zhao J, Wang Y, et al. Heparin- and Basic Fibroblast Growth Factor- incorporated Stent: A New Promising Method for Myocardial Revascularization[J]. J Surg Res. 2009 Jun 6.
[66] Wang Y, Liu XC, Zhang GW, et al. A new transmyocardial degradable stent combined with growth factor, heparin, and stem cells in acute myocardial infarction[J]. Cardiovasc Res. 2009, 84(3): 461-469.
[67] Yamamoto S, Kohmoto T, Kino K, et al.Potential Use of Ultrasound in Creating Transmyocardial Channels[J]. Jpn Circ J. 2001 , 65(6): 565-571.
[68] Heilmann CA, Attmann T, von Samson P, et al. Transmyocardial laser revascularization combined with vascular endothelial growth factor121 (VEGF121) gene therapy for chronic myocardial ischemia- do the effects really add up[J]? Eur J Cardiothorac Surg. 2003, 23(1): 74-80.
[69] Spiegelstein D, Kim C, Zhang Y,et al. Combined transmyocardial revascularization and cell-based angiogenic gene therapy increases transplanted cell survival[J]. Am J Physiol Heart Circ Physiol. 2007, 293(6): H3311-3316.
[70] Horvath KA, Smith WJ, Laurence RG, et al.Recovery and viability of an acute myocardial infarct after transmyocardial laser revascularization[J]. J Am Coll Cardiol. 1995, 25(1): 258-63.
[71] Arora RC, Hirsch GM, Hirsch K, et a1. Transmyocardial laser revascu1arization remodels the intrinsic cardiac nervous system in a chromic setting[J]. Circulation. 2001, 104(12): 1115-1120.
[72] Moses JW, Moussa I, Leon MB, et a1. Effect of catheter-based iridium-192 gamma brachytherapy on the added risk of restenosis from diabetes mellitus after intervention for in stent restenosis (subanalysis of the GAMMA I randomized triad[J]. Am J Cardiol. 2002, 90(3): 243-247.
[73] Li W, Chiba Y, Kimura T, et a1. Transmyocardial laser revascularization induced angiogenesis correlated with the expression of matrix metalloproteinases and platelet-derived endothelial cell growth factor[J]. Eur J Cardiothorac Surg. 2001, 19(2): 156-163.
[74] Almeda FQ, Glock D, Sandelski J, et al. The effect of percutaneous transmyocardial laser revascularization on left ventricular function in a porcine model of hibernating myocardium: a pilot study[J]. Cardiovasc Radiat Med. 2004 , 5(3): 132-135.
[75] Chen B, Dang J, Tan TL, et al. Dynamics of smooth muscle cell deadhesion from thermosensitive hydroxybutyl chitosan. Biomaterials. 2007, 28(8): 1503-1514.
[76] Freyman T, Polin G, Osman H, et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J. 2006 , 27(9):1114-1122.
[77] Savoye C, Equine O, Tricot O, et al. Left ventricular remodeling after anterior wall acute myocardial infarction in modern clinical practice (from the REmodelage VEntriculaire [REVE] study group) [J]. Am J Cardiol, 2006, 98(9): 1144-1149.
[78] Sakakibara Y, Tambara K, Sakaguchi G, et al. Toward surgical angiogenesis using slow-released basic fibroblast growth factor [J]. Eur J Cardiothorac Surg. 2003, 24(1): 105-111.
[79] Virag JA, Rolle ML, Reece J, et al. Fibroblast growth factor-2 regulates myocardial infarct repair: effects on cell proliferation, scar contraction, and ventricular function[J]. Am J Pathol. 2007, 171(5): 1431-1440.
[80] de Souza RR. Aging of myocardial collagen[J]. Biogerontology, 2002, 3(6): 325-335.
[81] Whittaker P. Unravelling the mysteries of collagen and cicatrix after myocardial infarction[J]. Cardiovasc Res. 1995, 29(6): 758-762.
[1] Sam J, Angoulvant D, Fazel S,et al. Heart cell implantation after myocardial infarction[J]. Coron Artery Dis, 2005 , 16(2): 85-91.
[2] Price MJ, Chou CC, Frantzen M, et al. Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties[J]. Int J Cardiol, 2006 , 111(2): 231-239.
[3] Newman CM, Bettinger T. Gene therapy progress and prospects: ultrasound for gene transfer[J]. Gene Ther, 2007 , 14(6): 465-475.
[4] Zen K, Okiqaki M, Hosokawa y, et al. Myocardium-targeted delivery of endothelial progenitor cells by ultrasound-mediated microbubble destruction improves cardiac function via an angiogenic response[J]. J Mol Cell Cardiol, 2006 , 40(6): 799-809.
[5] Iwatate M, Miura T, Ikeda Y, et al. Effects of in vivo gene transfer of fibroblast growth factor-2 on cardiac function and collateral vessel formation in the microembolized rabbit heart[J]. Jpn Circ J, 2001 , 5(3):226-231.
[6] Valina C, Pinkernell K, Song YH, et al. Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction[J]. Eur Heart J, 2007, 28(21): 2667-2677.
[7] Erbs S, Linke A, Sch?chinger V, et al. Restoration of Microvascular Function in the Infarct-Related Artery by Intracoronary Transplantation of Bone Marrow Progenitor Cells in Patients With Acute Myocardial Infarction[J]. Circulation, 2007 , 116(4): 366-374.
[8] vulliet PR, Greeley M, Halloran SM, et al. Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs[J]. Lancet, 2004, 363(9411): 783-784.
[9] Barbash IM, Chouraqui P, Baron J, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility,cell migration, and body distribution[J]. Circulation, 2003, 108(7): 863-868.
[10] Makela J, Ylitalo K, Lehtonen S, et al. Bone marrow-derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site[J]. Thorac Cardiovasc Surg, 2007 , 134(3): 565-573.
[11] Bouqioukas I, Didilis V, Ypsilantis P, et al. Intramyocardial injection of low-dose basic fibroblast growth factor or vascular endothelial growth factor induces angiogenesis in the infarcted rabbit myocardium[J]. Cardiovasc Pathol, 2007, 16(2): 63-68.
[12] Yau TM, Kim C, Li G, et al. Enhanced angiogenesis with multimodal cell-based gene therapy[J]. Ann Thorac Surg, 2007 , 83(3): 1110-1119.
[13] Tse HF, Siu CW, Zhu SG, et al. Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischaemic myocardium[J]. Eur J Heart Fail, 2007 , 9(8): 747-753.
[14] Beeres SL,Bax JJ,Dibbets-Schneider, et al.Intramyocardial injection of autologous bone marrow mononuclear cells in patients with chronic myocardial infarction and severe left ventricular dysfunction[J]. Am J Cardiol, 2007, 100(7):1094-1098.
[15] Gy?ngy?si M, Khorsand A, Sochor H, et al. Characterization of Hibernating Myocardium With NOGA Electroanatomic Endocardial Mapping[J]. Am Cardiol,2005, 95: 722–728.
[16] Kastrup J, Jorgensen E, Ruck A, et al. Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris A randomized double-blind placebo-controlled study: the Euroinject One trial[J]. J Am Coll Cardiol. 2005 , 45: 982-988.
[17] Hao X,Brace CJ,Pislaru C,et a1.Segmenting high frequency intracardiac ultrasound images of myocardium into infarcted,ischemic,and normal regions[J].IEEE Trans Med Imaging, 2001 , 20(12): 1373-1383.
[18] Park SW, Gwon HC, Geong GO,et al. Intracardiac echocardiographic guidance and monitoring during percutaneous endomyocardial gene injection in porcine heart[J].Hum Gene Ther, 2001 , 12(8): 893-903.
[19] Baklanov DV, de Muinck ED, Simons M, et al. Live 3D echo guidance of catheter-based endomyocardial injection[J].Catheter Cardiovasc Interv, 2005 , 65(3): 340-345.
[20] Rickers C,Gallegos R,Seethamraju RT, el a1.Applications of magnetic resonance imaging for cardiac stem cell therapy[J] . J Interv Cardiol, 2004 , 17(1): 37-46.
[21] Saeed M, Martin AJ, Lee RJ, et al. MR Guidance of Targeted Injections into Border and Core of Scarred Myocardium in Pigs[J]. Radiology, 2006, 240(2): 419-426.
[22] Freyman T, Polin G, Osman H,et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction[J]. Eur Heart J, 2006, 27(9): 1114-1122.
[23] de Silva RM,Gutiérrez LF,Raval AN,et al. X-Ray Fused With Magnetic Resonance Imaging (XFM)to Target Endomyocardial Injections: Validation in a Swine Model of Myocardial Infarction[J]. Circulation, 2006, 114(22): 2342-2350.
[24] Matthews KG, Devlin GP, Stuart SP, et al. Intrapericardial IGF-I improves cardiac function in an ovine model of chronic heart failure[J]. Heart Lung Circ, 2005 , 14(2): 98-103.
[25] Hayashi M, Li TS, Ito H, et al. Comparison of intramyocardial and intravenous routes of delivering bone marrow cells for the treatment of ischemic heart disease: an experimental study[J]. Cell Transplant, 2004, 13: 639-647.
[26] Grogaard HK, Sigurjonsson OE, Brekke M, et al. Cardiac accumulation of bone marrow mononuclear progenitor cells after intracoronary or intravenous injection in pigs subjected to acute myocardial infarction with subsequent reperfusion[J]. Cardiovasc Revasc Med, 2007 , 8(1): 21-27.
[27] Perin EC, Silva GV, Assad JA,et al. Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction[J]. J Mol Cell Cardiol,2008, 44(3): 486-495.
[28] Gavira JJ, Perez-Ilzarbe M, Abizanda G, et al. A comparison betweenpercutaneous and surgical transplantation of autologous skeletal myoblasts in a swine model of chronic myocardial infarction[J]. Cardiovasc Res, 2006, 71(4): 744-753.
[29]程芮,王士雯,张友荣,等.3种不同途径移植自体骨髓间充质干细胞治疗急性心肌梗死效果比较[J].中华实验外科杂志,2005,22(l2):1504-1506.
[30] Tse HF, Thambar S, Kwong YL, et al. Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases[J]. Eur Heart J, 2007 ,28(24): 2998-3005.
[2] Gassler N, Stubbe HM. Clinical data and histological features of transmyocardial revascularization with CO2-laser [J]. Eur J Cardiothorac Surg. 1997, 12(1): 25-30.
[3] Mueller XM, Tevaearai HT, Chaubert P, et al. Does laser injury induce a different neovascularisation pattern from mechanical or ischaemic injuries [J]? Heart. 2001, 85(6): 697-701.
[4] Huikeshoven M, Beli?n JA, Tukkie R, et al. The vascular response induced by transmyocardial laser revascularization is determined by the size of the channel scar: Results of CO2, holmium and excimer lasers [J]. Lasers Surg Med. 2004, 35(1): 35-40.
[5] Tasse J, Arora R. Transmyocardial revascularization: peril and potential[J]. J Cardiovasc Pharmacol Ther. 2007, 12(1): 44-53.
[6] Briones E, Lacalle JR, Marin I. Transmyocardial laser revascularization versus medical therapy for refractory angina [J]. Cochrane Database Syst Rev. 2009, 21 (1): CD003712.
[7] Chu VF, Giaid A, Kuang JQ, et a1. Thoracic Surgery Directors Association Award. Angiogenesis in transmyocardial revascularization: comparison of laser versus mechanical punctures [J]. Ann Thorae Surg. 1999, 68(2):301-307.
[8] Mack CA, Magovern CJ,Hahn RT,et al. Channel patency and neovascularization after transmyocardial revascularlzation using an excimer laser, results and comparisons to nonlased channels [J]. Circulation. 1997, 96(9): II65- II69.
[9] Whittaker P. Transmyocardial revascularization: the fate of myocardial channels [J]. Ann Thorac Surg. 1999, 68(6): 2376-2382.
[10] Arora A, Hakim I, Baxter J,et al. Needle-free delivery of macromolecules across the skin by nanoliter-volume pulsed microjets [J]. Proc Natl Acad Sci U S A. 2007, 104(11): 4255-4260.
[11]吴俊,孙俊英.软骨组织工程支架材料研究进展[J].中国矫形外科杂志. 2004, 12(3,4): 282-284.
[12] Wagner S, Dues G, Sawitzky D,et al. Assessment of the biological performance of the needle-free injector INJEX using the isolated porcine forelimb[J]. Br J Dermatol. 2004, 150(3): 455–461.
[13] Normand V, Lootens DL, Amici E. New insight into agarose gel mechanical properties[J]. Biomacromolecules. 2000, 1(4), 730-738.
[14] Figge FH,Barnett DJ. Anatomic evaluation of a jet injection instrument designed to minimize pain and inconvenience of parenteral therapy[J]. Am Pract Dig Treat. 1948, 3 (4): 197– 206.
[15] Perkin FS. Jet injection of insulin in treatment of diabetes mellitus[J]. Proc Am Diabetes Assoc. 1950, 10: 185–199.
[16] Hingson RA, Davis HS, Rosen M. Historical development of jet injection and envisioned uses in mass immunization and mass therapy based upon 2 decades experience[J]. Mil Med. 1963,128(6): 516.
[17] Choi AH, Smiley K, Basu M, et al. Protection of mice against rotavirus challenge following intradermal DNA immunization by Biojector needle-free injection[J]. Vaccine , 2007, 25 (16):3215-3218.
[18] Baxter J, Mitragotri S. Needle-free liquid jet injections: mechanisms and applications[J]. Expert Rev Med Devices. 2006, 3 (5): 565-574.
[19] Benedek K, Walker E, Doshier LA, et al. Studies on the use of needle-free injection device on proteins[J]. J Chromatogr A, 2005, 1079 (1-2): 397-407.
[20] Schramm-Baxter J, Mitragotri S. Needle-free jet injections: dependence of jet penetration and dispersion in the skin on jet power[J]. J Control Release. 2004, 97(3): 527-535.
[21]石卫东,刘美含,李新颖等.定量组织速度成像及组织追踪成像技术与MRI检查评价急性心肌梗死犬左室壁节段性运动异常的对照研究[J].吉林医学,2009,30(19):2235-2239.
[22] Modersohn D, Eddicks S, Ast I, et al. Influence of transmyocardial laser revascularization (TMLR) on regional cardiac function and metabolism in an isolated hemoperfused working pig heart[J]. Int J Artif Organs, 2002, 25( 11): 1074-1081.
[23] Lu WN, LüSH, Wang HB, et a1. Functional improvement of infarcted heart by co-Injection of embryonic stem cells with temperature-responsive chitosan hydrogel[J]. Tissue Eng Part A. 2009, 15(6): 1437-1447.
[24] Allen KB, Kelly J, Borkon AM, et a1. Transmyocardial laser revascularization: from randomized trials to clinical practice. A review of techniques, evidence-based outcomes, and future directions[J]. Anesthesiol Clin, 2008, 26(3): 501-519.
[25] Cooley DA, Frazier OH, Kadipasaoglu KA, et a1. Transmyocardial laser revascu- larization:anatomic evidence of long-term channel potency[J ]. Texas Heart Inst J. 1994, 21(3): 220-224.
[26] Domkowski PW, Biswas SS, Steenbergen C, et a1. Histological evidence of anglogenesis 9 months after transmyocardial laser revascularization[J]. Circulation. 2001, 103(3): 469-471.
[27]李长青,周跃.椎间盘组织工程支架材料研究进展[J].中国修复重建外科杂志, 2005, 19(12): 1033-1035.
[28]王伟,范明,智小东等.神经支架复合体修复周围神经缺损[J].中国医学科学院学报, 2005, 279(6): 688-669.
[29] Bensaid W, Triffitt JT, Blanchat C, et al. A biodegradable fibrin scaffold for mesenchymal stem cell transplantation[J]. Biomaterials. 2003, 24(14): 2497-2502.
[30] Yu J, Christman KL, Chin E, et al. Restoration of left ventricular geometry and improvement of left ventricular function in a rodent model of chronic ischemic cardiomyopathy[J]. J Thorac Cardiovasc Surg. 2009, 137(1): 180-187.
[31] Mukherjee R, Zavadzkas JA, Saunders SM, et al. Targeted myocardial microinjections of a biocomposite material reduces infarct expansion in pigs[J].Ann Thorac Surg. 2008, 86(4): 1268-1276.
[32]朱向明,王新房,刘望彭,等.激光心肌打孔隧道埋植bFGF缓释胶对急性缺血心肌血管生成及血流灌注的影响[J].中国超声医学杂志, 2004, 20(1): 4-8.
[33] Jiang T, Kumbar SG, Nair LS, et al. Biologically active chitosan systems for tissue engineering and regenerative medicine[J]. Curr Top Med Chem. 2008, 8(4): 354-364.
[34] Kang GD, Song SC. Effect of chitosan on the release of protein from thermosensitive poly(organophosphazene) hydrogels[J]. Int J Pharm. 2008, 349(1-2): 188-195.
[35] Xia P, Hou C, Wang W. Inhibitive effects of chitosan on proliferation of fibroblasts in vitro[J]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2007, 21(8): 833-836.
[36] Molinaro G, Leroux JC, Damas J, et al. Biocompatibility of thermosensitive chitosan-based hydrogels: an in vivo experimental approach to injectable biomaterials[J]. Biomaterials. 2002 , 23(13): 2717-2722.
[37] Mori T, Okumura M, Matsuura M, et al. Effects of chintin and its derivatives on the proliferation and cytokine production of fibroblasts in vivo[J]. Biomaterials. 1997 , 18(13): 947-951.
[38] Ahmed TA, Dare EV, Hincke M. Fibrin: A Versatile Scaffold for Tissue Engineering Applications[J]. Tissue Eng PartB Rev. 2008 May 1.
[39]朱爱萍,吴钧,张娜等.壳聚糖-一种具有应用潜力的组织工程支架材料.化学通报, 2002, 65(3): 1-5.
[40] Zardini P. Left ventricular remodeling after myocardial infarction [J]. Cardiologia. 1995, 40(11): 801-802.
[41] Simons M, Annex BH, Laham RJ, et al. Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: double-blind, randomized, controlled clinical trial[J] . Circulation. 2002 , 105(7): 788-793.
[42] Yl?-Herttuala S, Rissanen TT, Vajanto I, et al. Vascular endothelial growth factors: biology and current status of clinical applications in cardiovascular medicine[J]. J Am Coll Cardiol. 2007, 49(10): 1015-1026.
[43] Kim IY, Seo SJ, Moon HS, et al. Chitosan and its derivatives for tissueengineering applications[J]. Biotechnol Adv, 2008, 26(1): 1-21.
[44] Nguyen MK, Lee DS. Injectable Biodegradable Hydrogels[J]. Macromol Biosci. 2010 Mar 1.
[45] Desai PN, Yuan Q, Yang H. Synthesis and characterization of photocurable polyamidoamine dendrimer hydrogels as a versatile platform for tissue engineering and drug delivery[J]. Biomacromolecules. 2010, 11(3): 666-673.
[46] de Veies C , Escobedo JA ,Ueno H , et al. The fms - like tyrosine kinase , a receptor for vascular endothelial growth factor[J]. Science. 1992, 255(5047): 989-991.
[47] Yu PJ, Ferrari G, Galloway AC, et al. Basic fibroblast growth factor (FGF-2): the high molecular weight forms come of age[J]. J Cell Biochem. 2007,100(5): 1100-1108.
[48] Detillieux KA, Sheikh F, Kardami E ,et al. Biological activities of fibroblast growth factor-2 in the adult myocardium[J]. Cardiovasc Res. 2003 , 57(1): 8-19.
[49] Shao ZQ, Takaji K, Katayama Y, et al. Effects of intramyocardial administration of slow-release basic fibroblast growth factor on angiogenesis and ventricular remodeling in a rat infarct model[J]. Circ J. 2006 , 70(4): 471-477.
[50] Boodhwani M, Sodha NR, Laham RJ, et al. The future of therapeutic myocardial angiogenesis[J]. Shock. 2006 , 26(4): 332-341.
[51] Kano MR, Morishita Y, Iwata C, et al. VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B-PDGFRbeta signaling[J]. J Cell Sci. 2005, 118(16): 3759-3768.
[52]温铭杰,刘冰,孙丽翠等.人VEGF165和bFGF基因联合治疗大鼠急性心肌梗死.首都医科大学学报[J]. 2006, 27(5): 627-630.
[53] Yau TM, Kim C, Li G, et al. Enhanced angiogenesis with multimodal cell-based gene therapy[J]. Ann Thorac Surg. 2007, 83(3): 1110-1119.
[54] Layman H, Sacasa M, Murphy AE,et al. Co-delivery of FGF-2 and G-CSF from gelatin-based hydrogels as angiogenic therapy in a murine critical limb ischemic model[J]. Acta Biomater. 2009, 5(1): 230-239.
[55] Lu H, Xu X, Zhang M,et al. Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs[J]. Proc Natl Acad Sci U S A. 2007, 104(29): 12140-12145.
[56] Allen KB, DoMing RD, Angell ww, et a1. Transmyocardial revaseulafization: 5-year follow-up of a prospective, randomized multicenter trial[J]. Ann Thorac Snrg. 2004, 77(4): 1228-1234.
[57] Mueller XM, Tevaearai HT, Genton CY, et a1. Improved neoangiogenesis in transmyocardial laser revascularization combined with adjunct in a pig model [J]. Clin Sci(Lond). 2000, 99(6): 535-540.
[58] Tokura S, Tamura H, Azuma I. Immunological aspects of chitin and chitin derivatives administered to animals[J]. Exs .1999; 87: 279–292.
[59] Ishihara M, Obara K, Ishizuka T, et al . Controlled release of fibroblast growth factors and heparin from photocrosslinked chitosan hydrogels and subsequent effect on in vivo vascularization[J]. J Biomed Mater Res A . 2003, 64(3): 551-559.
[60] Cherian SM, Bobryshev YV, Tran D, et al. Cellular destruction following transmyocardial laser revascularization (TMR) [J]. J Mol Histol. 2005, 36(4) : 275-280.
[61] Chupa JM, Foster AM, Sumner SR, et al. Vascular cell responses to polysaccharide materials: in vitro and in vivo evaluations[J]. Biomaterials. 2000, 21(22): 2315-2322.
[62] Nakamura S, Nambu M, Ishizuka T, et al. Effect of controlled release of fibroblast growth factor-2 from chitosan/fucoidan micro complex-hydrogel on in vitro and in vivo vascularization[J]. J Biomed Mater Res A. 2008,85(3): 619-627.
[63] Yamamoto N, Kohmoto T, Roethy W, et a1. Histologic evidence that basic fibroblast growth factor enhances the angiogenic effects of transmyocardial laser revascularization [J]. Basic Res Cardiol. 2000, 95(1): 55-63.
[64]朱向明,王新房,刘望彭等.激光心肌打孔隧道埋植bFGF缓释胶对急性缺血心肌血管生成及血流灌注的影响[J].中国超声医学杂志. 2004, 20(1): 4-8.
[65] Liu XC, Zhao J, Wang Y, et al. Heparin- and Basic Fibroblast Growth Factor- incorporated Stent: A New Promising Method for Myocardial Revascularization[J]. J Surg Res. 2009 Jun 6.
[66] Wang Y, Liu XC, Zhang GW, et al. A new transmyocardial degradable stent combined with growth factor, heparin, and stem cells in acute myocardial infarction[J]. Cardiovasc Res. 2009, 84(3): 461-469.
[67] Yamamoto S, Kohmoto T, Kino K, et al.Potential Use of Ultrasound in Creating Transmyocardial Channels[J]. Jpn Circ J. 2001 , 65(6): 565-571.
[68] Heilmann CA, Attmann T, von Samson P, et al. Transmyocardial laser revascularization combined with vascular endothelial growth factor121 (VEGF121) gene therapy for chronic myocardial ischemia- do the effects really add up[J]? Eur J Cardiothorac Surg. 2003, 23(1): 74-80.
[69] Spiegelstein D, Kim C, Zhang Y,et al. Combined transmyocardial revascularization and cell-based angiogenic gene therapy increases transplanted cell survival[J]. Am J Physiol Heart Circ Physiol. 2007, 293(6): H3311-3316.
[70] Horvath KA, Smith WJ, Laurence RG, et al.Recovery and viability of an acute myocardial infarct after transmyocardial laser revascularization[J]. J Am Coll Cardiol. 1995, 25(1): 258-63.
[71] Arora RC, Hirsch GM, Hirsch K, et a1. Transmyocardial laser revascu1arization remodels the intrinsic cardiac nervous system in a chromic setting[J]. Circulation. 2001, 104(12): 1115-1120.
[72] Moses JW, Moussa I, Leon MB, et a1. Effect of catheter-based iridium-192 gamma brachytherapy on the added risk of restenosis from diabetes mellitus after intervention for in stent restenosis (subanalysis of the GAMMA I randomized triad[J]. Am J Cardiol. 2002, 90(3): 243-247.
[73] Li W, Chiba Y, Kimura T, et a1. Transmyocardial laser revascularization induced angiogenesis correlated with the expression of matrix metalloproteinases and platelet-derived endothelial cell growth factor[J]. Eur J Cardiothorac Surg. 2001, 19(2): 156-163.
[74] Almeda FQ, Glock D, Sandelski J, et al. The effect of percutaneous transmyocardial laser revascularization on left ventricular function in a porcine model of hibernating myocardium: a pilot study[J]. Cardiovasc Radiat Med. 2004 , 5(3): 132-135.
[75] Chen B, Dang J, Tan TL, et al. Dynamics of smooth muscle cell deadhesion from thermosensitive hydroxybutyl chitosan. Biomaterials. 2007, 28(8): 1503-1514.
[76] Freyman T, Polin G, Osman H, et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J. 2006 , 27(9):1114-1122.
[77] Savoye C, Equine O, Tricot O, et al. Left ventricular remodeling after anterior wall acute myocardial infarction in modern clinical practice (from the REmodelage VEntriculaire [REVE] study group) [J]. Am J Cardiol, 2006, 98(9): 1144-1149.
[78] Sakakibara Y, Tambara K, Sakaguchi G, et al. Toward surgical angiogenesis using slow-released basic fibroblast growth factor [J]. Eur J Cardiothorac Surg. 2003, 24(1): 105-111.
[79] Virag JA, Rolle ML, Reece J, et al. Fibroblast growth factor-2 regulates myocardial infarct repair: effects on cell proliferation, scar contraction, and ventricular function[J]. Am J Pathol. 2007, 171(5): 1431-1440.
[80] de Souza RR. Aging of myocardial collagen[J]. Biogerontology, 2002, 3(6): 325-335.
[81] Whittaker P. Unravelling the mysteries of collagen and cicatrix after myocardial infarction[J]. Cardiovasc Res. 1995, 29(6): 758-762.
[1] Sam J, Angoulvant D, Fazel S,et al. Heart cell implantation after myocardial infarction[J]. Coron Artery Dis, 2005 , 16(2): 85-91.
[2] Price MJ, Chou CC, Frantzen M, et al. Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties[J]. Int J Cardiol, 2006 , 111(2): 231-239.
[3] Newman CM, Bettinger T. Gene therapy progress and prospects: ultrasound for gene transfer[J]. Gene Ther, 2007 , 14(6): 465-475.
[4] Zen K, Okiqaki M, Hosokawa y, et al. Myocardium-targeted delivery of endothelial progenitor cells by ultrasound-mediated microbubble destruction improves cardiac function via an angiogenic response[J]. J Mol Cell Cardiol, 2006 , 40(6): 799-809.
[5] Iwatate M, Miura T, Ikeda Y, et al. Effects of in vivo gene transfer of fibroblast growth factor-2 on cardiac function and collateral vessel formation in the microembolized rabbit heart[J]. Jpn Circ J, 2001 , 5(3):226-231.
[6] Valina C, Pinkernell K, Song YH, et al. Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction[J]. Eur Heart J, 2007, 28(21): 2667-2677.
[7] Erbs S, Linke A, Sch?chinger V, et al. Restoration of Microvascular Function in the Infarct-Related Artery by Intracoronary Transplantation of Bone Marrow Progenitor Cells in Patients With Acute Myocardial Infarction[J]. Circulation, 2007 , 116(4): 366-374.
[8] vulliet PR, Greeley M, Halloran SM, et al. Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs[J]. Lancet, 2004, 363(9411): 783-784.
[9] Barbash IM, Chouraqui P, Baron J, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility,cell migration, and body distribution[J]. Circulation, 2003, 108(7): 863-868.
[10] Makela J, Ylitalo K, Lehtonen S, et al. Bone marrow-derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site[J]. Thorac Cardiovasc Surg, 2007 , 134(3): 565-573.
[11] Bouqioukas I, Didilis V, Ypsilantis P, et al. Intramyocardial injection of low-dose basic fibroblast growth factor or vascular endothelial growth factor induces angiogenesis in the infarcted rabbit myocardium[J]. Cardiovasc Pathol, 2007, 16(2): 63-68.
[12] Yau TM, Kim C, Li G, et al. Enhanced angiogenesis with multimodal cell-based gene therapy[J]. Ann Thorac Surg, 2007 , 83(3): 1110-1119.
[13] Tse HF, Siu CW, Zhu SG, et al. Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischaemic myocardium[J]. Eur J Heart Fail, 2007 , 9(8): 747-753.
[14] Beeres SL,Bax JJ,Dibbets-Schneider, et al.Intramyocardial injection of autologous bone marrow mononuclear cells in patients with chronic myocardial infarction and severe left ventricular dysfunction[J]. Am J Cardiol, 2007, 100(7):1094-1098.
[15] Gy?ngy?si M, Khorsand A, Sochor H, et al. Characterization of Hibernating Myocardium With NOGA Electroanatomic Endocardial Mapping[J]. Am Cardiol,2005, 95: 722–728.
[16] Kastrup J, Jorgensen E, Ruck A, et al. Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris A randomized double-blind placebo-controlled study: the Euroinject One trial[J]. J Am Coll Cardiol. 2005 , 45: 982-988.
[17] Hao X,Brace CJ,Pislaru C,et a1.Segmenting high frequency intracardiac ultrasound images of myocardium into infarcted,ischemic,and normal regions[J].IEEE Trans Med Imaging, 2001 , 20(12): 1373-1383.
[18] Park SW, Gwon HC, Geong GO,et al. Intracardiac echocardiographic guidance and monitoring during percutaneous endomyocardial gene injection in porcine heart[J].Hum Gene Ther, 2001 , 12(8): 893-903.
[19] Baklanov DV, de Muinck ED, Simons M, et al. Live 3D echo guidance of catheter-based endomyocardial injection[J].Catheter Cardiovasc Interv, 2005 , 65(3): 340-345.
[20] Rickers C,Gallegos R,Seethamraju RT, el a1.Applications of magnetic resonance imaging for cardiac stem cell therapy[J] . J Interv Cardiol, 2004 , 17(1): 37-46.
[21] Saeed M, Martin AJ, Lee RJ, et al. MR Guidance of Targeted Injections into Border and Core of Scarred Myocardium in Pigs[J]. Radiology, 2006, 240(2): 419-426.
[22] Freyman T, Polin G, Osman H,et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction[J]. Eur Heart J, 2006, 27(9): 1114-1122.
[23] de Silva RM,Gutiérrez LF,Raval AN,et al. X-Ray Fused With Magnetic Resonance Imaging (XFM)to Target Endomyocardial Injections: Validation in a Swine Model of Myocardial Infarction[J]. Circulation, 2006, 114(22): 2342-2350.
[24] Matthews KG, Devlin GP, Stuart SP, et al. Intrapericardial IGF-I improves cardiac function in an ovine model of chronic heart failure[J]. Heart Lung Circ, 2005 , 14(2): 98-103.
[25] Hayashi M, Li TS, Ito H, et al. Comparison of intramyocardial and intravenous routes of delivering bone marrow cells for the treatment of ischemic heart disease: an experimental study[J]. Cell Transplant, 2004, 13: 639-647.
[26] Grogaard HK, Sigurjonsson OE, Brekke M, et al. Cardiac accumulation of bone marrow mononuclear progenitor cells after intracoronary or intravenous injection in pigs subjected to acute myocardial infarction with subsequent reperfusion[J]. Cardiovasc Revasc Med, 2007 , 8(1): 21-27.
[27] Perin EC, Silva GV, Assad JA,et al. Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction[J]. J Mol Cell Cardiol,2008, 44(3): 486-495.
[28] Gavira JJ, Perez-Ilzarbe M, Abizanda G, et al. A comparison betweenpercutaneous and surgical transplantation of autologous skeletal myoblasts in a swine model of chronic myocardial infarction[J]. Cardiovasc Res, 2006, 71(4): 744-753.
[29]程芮,王士雯,张友荣,等.3种不同途径移植自体骨髓间充质干细胞治疗急性心肌梗死效果比较[J].中华实验外科杂志,2005,22(l2):1504-1506.
[30] Tse HF, Thambar S, Kwong YL, et al. Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases[J]. Eur Heart J, 2007 ,28(24): 2998-3005.