骨髓间充质干细胞移植与肝细胞生长因子转导对猪心肌梗死后心力衰竭治疗作用的比较

目的研究经猪非梗死相关动脉分别移植骨髓间充质干细胞(bone marrow-derivedmes-enchymal stem cells,BM-MSCs)或腺病毒介导肝细胞生长因子(adenovirus5-hepatocyte growth factor,Ad5-HGF)对心肌梗死的治疗作用。方法苏中幼猪18只,分为3组:BM-MSCs组、Ad5-HGF组与对照组。3组均经开胸结扎冠状动脉前降支制作心肌梗死模型。BM-MSCs组结扎后2周抽取骨髓分离培养BM-MSCs,并在结扎后4周经非梗死相关动脉注入梗死心脏(剂量5×106/mL)。Ad5-HGF组于结扎后4周经非梗死相关动脉注入Ad5-HGF4×109pfu。对照组则注入同样量的细胞培养液(IMDM)。三组均在结扎后4周和7周行门控心肌显像评价心肌灌注及心功能,并在7周处死动物,取心脏标本,行免疫组化检查。结果(1)免疫组化结果:在两治疗组与对照组梗死周边区均可见新生血管,BM-MSCs组和Ad5-HGF组的新生血管密度(毛细血管密度分别为102·4±8·6/mm2和105·3±7·7/mm2,功能血管密度分别为52·1±4·1/mm2和66·0±3·3/mm2)均高于对照组(毛细血管密度55·5±4·7/mm2,功能血管密度16·4±3·5/mm2),P均<0·01。(2)门控心肌显像:治疗后4周两治疗组及对照组间左室射血分数(LVEF)值差异均无统计学意义;治疗后7周BM-MSCs组和Ad5-HGF组LVEF值(45·0±2·7和43·9±4·3)明显优于对照组(30·4±2·8),差异均有统计学意义(P均<0·01);治疗组治疗后7周较4周时LVEF值明显好转(BM-MSCs组45·0±2·7比33·6±2·1,Ad5-HGF组43·9±4·3比32·2±1·8,P均<0·01),对照组前后LVEF值无明显变化;两治疗组LVEF值改善幅度相比,差异无统计学意义。结论经非梗死相关动脉移植BM-MSCs或Ad5-HGF均能促进梗死心脏心功能改善和促进血管再生,但未显示出二者之间何者更具优势。     

骨髓间充质干细胞联合肝细胞生长因子对心肌梗死治疗作用的实验研究

目的研究经非梗死相关动脉注入骨髓间充质干细胞(BMMSCS)联合肝细胞生长因子移植对心肌梗死的治疗作用。方法苏中幼猪18头,分为三组:单纯治疗组,联合治疗组及对照组,三组均经开胸结扎冠状动脉前降支制作心肌梗死模型,两组治疗组结扎后2周抽取骨髓分离培养骨髓间充质干细胞,并在结扎后4周经非梗死相关动脉注入梗死心肌(剂量5×106/ML),联合组同时注入肝细胞生长因子(HGF,4×109PFU),对照组则注入同样量的细胞培养液(IMDM);两组均在结扎后4周和8周行冠状动脉造影与门控心肌显像评价侧支循环和心功能,并在8周处死动物,取心脏标本,行免疫组化检查。结果(1)免疫组化结果显示:在两组治疗组与对照组梗死周边区均可见新生血管,但两组治疗组的新生血管密度高于对照组(P<0.05)。(2)门控心肌显像:治疗前两组治疗组与对照组LVEF无明显区别,无统计学意义(P>0.05);治疗后两组治疗组LVEF明显优于对照组,有统计学意义(P<0.05);两治疗组治疗前后LVEF明显好转(P<0.05),对照组前后LVEF无明显变化(P=0.035)。(3)冠状动脉造影显示:三组治疗前后侧支循环级别无统计学意义。结论经非梗死相关动脉BMMSCS联合肝细胞生长因子移植能够促进梗死心脏心功能改善和促进血管再生,但不能促进侧支血管的生成;同时联合治疗效果并不优于单纯干细胞治疗。     

经冠状动脉注射骨髓单个核细胞治疗缺血性心肌损伤的实验研究

目的　证实骨髓干细胞心肌内移植治疗对心脏功能的改善和促血管新生作用。方法　小型猪冠状动脉结扎制备心肌梗死模型 ,然后经冠状动脉内注射骨髓单个核细胞 ,术后 3周用超声心动图以及左心室造影检测心功能的变化 ,核素心肌显像观察心肌灌注的情况 ,冠状动脉造影观察侧支循环的形成 ,免疫组化计数血管密度。结果　心肌梗死小型猪冠状动脉注射骨髓单个核细胞后 ,左心室造影显示左室 dP dtmax与对照组比较增高。核素心肌显像显示冠状动脉注射骨髓单个核细胞后心肌灌注显著改善。移植治疗后冠状动脉造影显示有侧支循环形成 ,血管密度计数比对照组增加了5 2 2 % (5 6 6± 11 7 mm2 vs 37 2± 8 4 mm2 ,P <0 0 5 )。结论　骨髓单个核细胞心肌内移植可能通过促进血管新生改善心脏收缩功能。     

肝细胞生长基因转染诱导肺高压模型动物肺血管生成的实验研究

目的 在家兔高动力性肺动脉高压模型上经气管途径转染携带人肝细胞生长因子基因的重组腺病毒(Ad-HGF),探讨外源HGF基因转染诱导侧支肺血管生成的可行性.方法 1月龄幼兔正中开胸,行左无名动脉与主肺动脉吻合,通过持续左向右分流,3个月后建立高动力性肺动脉高压模璎.将模型动物随机分为对照组、GFP转染组、单次HGF治疗组和重复HGF治疗组.HGF治疗组(单次或1周后重复)通过气管内滴入的方法转染Ad-HGF.2周后,通过RT-PCR和免疫组织化学检测HGF基因和蛋白表达.分别在基因转染后14 d和30 d通过免疫组织化学榆测肺微血管和小动脉密度.1个月时,肺血管造影观测侧支血管建立情况.结果 气管内滴入Ad-HGF后2周,肺组织RNA提取后凝胶电泳显示有484 bp长的特异性片段出现,免疫组化町检测到肺血管内皮、肺泡上皮细胞内HGF表达.肺组织病理切片观察可见HGF基因治疗组肺血管密度(单次HGF治疗组和重复HGF治疗组)明显高于对照组和GFP转染组,增多的血管以微血管为主,1个月后,肌性肺动脉明显增多.肺血管造影证实HGF基因治疗组侧支血管较对照组和GFP转染组丰富.结论 外源性HGF基因经气管转染,早期(2周内)以诱导肺微血管新生为主,后期(1个月时)可促进肺小动脉生成.     

肝细胞生长因子抑制慢性缺血性心脏病心肌纤维化及心肌细胞凋亡的实验研究

目的:研究肝细胞生长因子（HGF）抑制慢性缺血性心脏病心肌纤维化及心肌细胞凋亡的作用。方法: 采用磷酸钙/DNA-TPC方法构建携带HGF基因的重组腺病毒(Ad.HGF)。经18只小型猪的左胸冠状动脉回旋支放置Ameroid环建立慢性心肌缺血猪动物模型,并随机分为3组即盐水组、AdHGF组和缺陷型空病毒Ad5(AdNull)组,每组6只(n=6)。于缺血心肌处,分别注射4×109 pfu 200 μl AdHGF、4×109 pfu 200 μl AdNull及200 μl盐水。4周后做超声心动图检查各组的心脏功能,并行病理学心肌纤维化、心肌凋亡检测。结果: 心脏彩超检测显示,AdHGF组室壁增厚,运动增加,左室舒张末容积（LVEDV）、左室射血分数（LVEF）及短轴缩短率（FS）等明显改善(P<0.05)。AdHGF组心肌组织切片缺血坏死区纤维组织增生明显低于AdNull组(P<0.05)。AdHGF组心肌中Ⅲ型胶原蛋白的量明显低于AdNull组(P<0.05)。AdHGF组心肌细胞的凋亡率(%)明显低于对照组(P<0.05)。结论: HGF具有抑制慢性缺血性心脏病心肌纤维化及心肌细胞凋亡的作用,从而可抑制心室重构和改善心功能。     

经冠状动脉注射骨髓单个核细胞影响心肌细胞凋亡的实验研究

目的观察经冠状动脉注射方式移植骨髓单个核细胞对心脏功能的改善和心肌细胞凋亡的影响。方法结扎小型猪冠状动脉制备心肌梗死模型，然后经冠状动脉注射骨髓单个核细胞，术后3周用超声心动图以及左心室造影检测心功能．核素心肌显像观察心肌灌注，冠状动脉造影观察侧支循环形成．用TUNEL检测心肌细胞凋亡。结果把骨髓单个核细胞通过冠状动脉注射到猪心肌梗死模型，显示左心室dp／dtmax较对照组增高，心肌灌注显著改善。冠状动脉有侧支循环形成，缺血心肌细胞；较对照组减少了53．6％结论骨髓单个核细胞心肌内移植可改善心脏收缩功能，可能与移植细胞抑制心肌细胞凋亡有关。     

冠状动脉侧支循环某些相关因素的临床研究

目的研究冠状动脉侧支循环在冠状动脉完全闭塞与次全闭塞血管病变中的形成情况,观察心肌梗死病史、心肌肥厚及糖尿病对侧支循环形成的影响以及侧支循环对心肌的保护作用。方法回顾分析了我院一年内409例经冠状动脉造影证实的冠状动脉完全或次全闭塞患者,先按有无心肌梗死病史将患者分为两组,对照分析侧支循环形成的良好率,及心功能相关因素方面的差异。再按有无心肌肥厚、有无糖尿病病史分别分为两组,观察其对侧支循环形成的影响。结果冠状动脉完全与次全闭塞对比侧支循环形成的良好率有显著差异。有心肌梗死与无心肌梗死病史两组侧支循环形成的良好率比较无显著差异。两组的左心室舒张末期内径、左心室射血分数、室壁运动异常发生率及室壁瘤形成均有显著差异。而有心肌梗死病史者侧支循环良好组与不良组比较左心室舒张末期内径、左心室射血分数无差异。有无心肌肥厚对侧支循环形成良好率无差异。有糖尿病史者侧支循环血流良好率明显高于无糖尿病史者,且有显著差异。结论冠状动脉侧支循环的开放依赖于冠状动脉血管的完全或次全闭塞。冠状动脉缓慢闭塞下形成的侧支循环对心肌、心功能有保护作用。糖尿病有利于侧支循环的发展。     

碱性成纤维细胞生长因子基因对猪缺血心肌侧支血管生成的作用

目的探讨经导管冠状动脉内注射碱性成纤维细胞生长因子(bFGF)基因(pcDNA3-bFGF)对猪缺血心肌侧支血管生成的作用。方法实验猪分为3组:手术对照组(n=6)、bFGF基因左冠状动脉注射组(n=6)和bFGF基因右冠状动脉注射组(n=6)。开胸结扎冠状动脉左回旋支(LCX),建立急性心肌梗死动物模型。术后2周,分别行选择性冠状动脉造影,并经导管冠状动脉内注射pcD-NA3-bFGF 2 000μg。给药后2周,再次行选择性冠状动脉造影观察冠状动脉侧支血管形成情况,并通过病理切片光镜观察、免疫组化染色进行血管计数,观察猪缺血心肌侧支血管生成情况。结果(1)病理切片及免疫组化染色结果显示左、右冠状动脉注射基因组血管计数较对照组明显增加;(2)术后4周选择性冠状动脉造影显示左、右冠状动脉注射基因组侧支血管明显多于对照组,左冠状动脉注射基因组侧支血管多于右冠状动脉基因注射组。结论经导管冠状动脉内注射bFGF基因能促进猪缺血心肌侧支血管生成。     

转染Angiopoietin-1基因对急性心梗后左室功能的影响

目的探讨重组腺病毒载体介导的血管形成素1(Ang1)基因转染对兔急性心梗后左室功能影响。方法构建含有Ang1的腺病毒粘粒载体,通过转染293细胞进行同源重组制备重组腺病毒颗粒。64只雄性新西兰大白兔行高位冠状动脉结扎,4只用于急性心梗后循环中VEGF含量的检测,其余60只随机均分为实验组、单纯培养基组(DMEM)与LacZ重组腺病毒组,分别于冠状动脉结扎后心肌内直接注射Ang1重组腺病毒,DMEM与LacZ重组腺病毒。并于转染后第3、14、28d应用超声心动图观察心功能情况,第3、7、14、28d应用RT PCR方法测定重组腺病毒基因在转染心肌中的表达,第14、28d用免疫组化方法观察缺血心肌内血管生长情况。结果获得的Ang1重组腺病毒滴度为5.6×1011pfu/L。重组腺病毒直接注射转染兔缺血心肌后能有效表达目的基因,RT PCR测定提示Ang1基因转染后第3d心肌中即有表达,7、14d仍呈阳性表达,28d未测出。心肌梗死后Ang1组心功能从术后第3d至第28d得到明显改善,其幅度显著好于对照组。心肌梗死后左室心肌收缩期截面积与舒张期截面积均明显增加,尤以术后第3d为著,随时间延长均有所缩小,至28d后Ang1组缩小幅度明显高于其他两组。转染14、28d后Ang1组新生毛细血管密度及αSMA阳性的小动脉性血管密度均明显高于对照组(P<0.01)。结论腺病毒介导的Ang1基因在兔缺血心肌中能有效地促进新生血管形成,并能改善缺血心肌的功能。     

重组腺病毒介导的血管生成素改善缺血性心脏病的实验研究

目的观察重组腺病毒介导的血管生成素促进慢性缺血心肌血管生成,并改善心肌血流灌注和心功能的有效性。方法置Ameriod环建立猪慢性心肌缺血模型,并随机分为3组,血管生成素腺病毒组,空病毒组,对照组。分别心内注射腺病毒介导的血管生成素基因、空病毒和生理盐水。通过冠状动脉造影、心脏超声、核磁心肌灌注成像、病理学观察等评价血管生成素的治疗效果。结果置环后的猪均为有效的动物模型。注射血管生成素的缺血心肌模型侧支血管增生明显,血管计数增加,Rentrop分数、面积变化分数改善,梗死区缩小,缺血区血管密度增高尤其是内皮细胞、平滑肌细胞增加,凋亡细胞减少、细胞之间的黏附性增加。结论腺病毒介导的血管生成素基因治疗缺血性心脏病可明显改善心功能,使局部血液循环明显改善。     

碱性成纤维细胞生长因子基因对猪缺血心肌心功能的影响

目的探讨经导管冠状动脉内注射碱性成纤维细胞生长因子基因(pcDNA3-bFGF),对猪缺血心肌心功能的影响。方法构建真核表达质粒pcDNA3-bFGF。开胸结扎猪冠状动脉左回旋支(LCX),建立急性心肌梗死动物模型。实验动物分为三组:手术对照组(n=6),bFGF基因左冠状动脉注射组(n=6),bFGF基因右冠状动脉注射组(n=6)。术后2周,分别行选择性冠状动脉造影,并经导管冠状动脉内注射pcDNA3-bFGF2000μg。术后4周,通过超声心动图测定左心室射血分数(LVEF),评估左心室收缩功能,并再次行选择性冠状动脉造影,观察冠状动脉侧枝血管新生情况,并通过压力监测装置观察不同组动物左心室舒张末压(LVEDP)。结果(1)术后4周超声心动图示左、右冠状动脉注射基因组LVEF值高于手术对照组,LVDEP低于手术对照组;(2)选择性冠状动脉造影显示,术后4周左右冠状动脉注射基因组侧枝血管明显多于对照组,左冠状动脉注射基因组,侧枝血管多于右冠状动脉基因注射组。结论经导管冠状动脉内注射bFGF基因,能促进猪缺血心肌血管新生,改善缺血心肌血供,改善心功能。     

直接心肌植入VEGF_(165)基因的实验研究

目的 :评估VEGF1 6 5基因直接心肌内注射促进心肌血运重建的疗效。方法 :中国实验小型猪 11只 ,体重 (2 9 3± 4 3)kg。在左冠状动脉回旋支 (LCX)近心端放置Ameroid收缩环。术后 6周行冠脉造影示LCX狭窄 >95 %为慢性心肌缺血模型形成。将选用模型随机分为治疗组 (n =6 )和对照组 (n =5 )。治疗组将VEGF1 6 5质粒注射到左室侧壁 10处有标记的心肌中层。对照组只注射空白质粒。治疗前和治疗 6周后 ,采用体表超声心动图观察静息与小剂量多巴酚丁胺负荷 (LDDSE)状态下左心室壁运动及功能 (LVEF、RT、MVCF、WMSI) ,通过2 0 1 TI SPECT观察心肌灌注改变。处死动物后进行心肌血管密度和VEGF基因mRNA表达测定。结果 :治疗 6周后 ,在静息与LDDSE(10 μg min kg)状态下 ,A组RT和WMSI较治疗前显著改善 ,侧壁灌注缺损明显缩小 ,B组改善不明显。A组每个视野的血管面积、血管周长及血管数目均较B组多。A组 2 3例局部心肌VEGF基因mRNA的表达明显 ,B组 3 3例均无表达。结论 :直接心肌内注射VEGF1 6 5基因可促进慢性缺血心肌的血管再生 ,改善局部心肌灌注和室壁运动。     

Adeno-associated virus vector-mediated production of hepatocyte growth factor attenuates liver fibrosis in mice

Purpose Adeno-associated virus (AAV) vectors can achieve long-term gene expression and are now feasible for use in human gene therapy. We constructed hepatocyte growth factor (HGF) expressing AAV (AAV5-HGF) and examined its effect in two mouse hepatic fibrosis models. Methods A model of hepatic fibrosis was established by carbon tetrachloride (CCl₄) administration in Balb/c mice. After the establishment of liver fibrosis, AAV5-HGF was injected once into the portal vein. Mice were killed 3, 6, 9, and 12 weeks after injection. Another model was established by bile duct ligation (BDL). Seven weeks after AAV5-HGF injection, mice underwent BDL, and were then killed 2 weeks after BDL. Results Mice that received AAV5-HGF achieved stable HGF expression both in the serum and liver for at least 12 weeks. In both models, significant improvement of the liver fibrosis was found in all mice receiving AAV5-HGF based on Azan-Mallory staining. Suppression of hepatic stellate cells (HSC) was confirmed by immunohistochemistry. Fibrogenic markers were significantly suppressed and collagenase activity increased in the livers of mice receiving AAV5-HGF. Conclusions A single injection of AAV vector containing HGF gene achieved long-term expression of HGF and resulted in resolution of mouse liver fibrosis. HGF gene therapy mediated by AAV is feasible for the treatment of liver fibrosis.     

Coronary collateral vessels: Their significance for left ventricular histologic structure

Whether coronary collateral vessels protect the left ventricular myocardium is unknown. Light microscopic morphometry was carried out on myocardial tissue samples from 56 surgically treated patients with coronary artery disease. Transmural biopsy of the myocardium perfused by the left anterior descending coronary artery was obtained during open heart surgery. In initial reproducibility studies of biopsy samples of 17 patients a sampling error for evaluation of myocardium was defined and differences in transmural fibrosis exceeding ±6.2 percent were considered biologically significant. Stenosis of the left anterior descending artery was determined from preoperative angiography. Group A (control group) comprised patients with less than 75 percent area reduction of the left anterior descending coronary artery (mean ± standard deviation 65 ±10 percent). Patients in group B (more than 95 percent area reduction [mean 99 ± 2 percent] without collateral supply on arteriography) were compared with patients in group C (identical stenosis [mean 99 ± 2 percent] but with collateral supply). Fibrosis averaged 17 percent in group A, 68 percent in group B (p < 0.001 versus group A) and 29 percent in group C (p > 0.05 versus group A, p < 0.001 versus group B). Thus, in severe coronary stenosis myocardium supplied by collateral vessels shows less fibrosis on biopsy sample than does myocardium without collateral supply.     

联合基因治疗小型猪冠状动脉闭塞的实验研究

目的　探讨联合血管内皮生长因子 (VEGF)及促血管生成素 1(Ang 1)基因治疗小型猪冠脉闭塞的疗效。方法　在小型猪冠脉闭塞模型的心肌内注射质粒PCD2 /VEGF和 (或 )PCD2 /Ang 1,检测外源基因在心肌中的表达并观察其生物学作用。结果　逆转录 PCR及免疫组化染色均检测到外源基因的表达。转PCD2 /VEGF和 (或 )PCD2 /Ang 1基因治疗组毛细血管计数及小动脉计数均高于空载质粒对照组 (P <0 0 5 ) ,联合基因治疗组血管计数最高。冠状动脉造影证明联合基因治疗组促进闭塞冠脉侧支循环建立更为有效。结论　心肌内联合注射PCD2 /VEGF及PCD2 /Ang 1基因能够获得外源基因mRNA及蛋白的有效表达 ,与单基因治疗相比联合基因治疗能更有效地促进血管生成及侧支循环的建立。     

Local dilatory reserve in chronic experimental coronary occlusion without infarction. Quantitation of collateral development

The local dilatory reserve of the canine coronary vasculature was studied with the particle distribution technique. Normal ventricles and hearts with slowly progressive narrowing of both the left circumflex coronary artery and the right coronary artery were studied. In spite of chronic occlusion of 2 coronary arteries myocardial infarction did not occur in the majority of animals because of collateral development. Coronary reserve was determined by producing graded to maximal coronary vasodilation. In normal hearts flow increased homogeneously over the entire left ventricle. In hearts with chronic coronary occlusion coronary vasodilation produced non-homogeneous increases in flow: collateral dependent myocardium received less blood flow than myocardium supplied by normal coronary arteries. Early after coronary occlusion the total coronary reserve was less than normal and the dilatory reserve of collateral dependent vessels was markedly diminished. Late (6 months) after coronary occlusion the total coronary reserve was still below normal but the dilatory reserve of collateral dependent vessels had improved. A new quantitative index of collateral function is defined as the level of coronary flow (delivered through normal coronary arteries) at which collateral flow deviates from homogeneous perfusion. Collateral function, when so defined, increases by a factor of almost 6 times between 4 weeks (early after coronary occlusion) and 6 months (late after occlusion) after the implantation of occluding devices.     

Myocardial viability in asynergic regions subtended by occluded coronary arteries: Relation to the status of collateral flow in patients with chronic coronary artery disease

Objectives. This study aimed to determine whether angiographically visualized collateral vessels in patients with chronic coronary artery disease imply the presence of viable myocardium in asynergic regions subtended by completely occluded coronary arteries.Background. Patients with chronic coronary artery disease who are being considered for revascularization frequently exhibit angiographically visualized collateral vessels to completely occluded coronary arteries supplying seventy asynergic myocardial regions. However, little is known about the relation between angiographic collateral flow and myocardial viability in these patients.Methods. We studied 42 patients with 78 completely occluded coronary arteries supplying asynergic territories. Angiographic collateral vessels were interpreted as absent (grade 1) in 14 patients, minimal (grade 2) in 27 and well developed (grade 3) in 37. Myocardial viability was determined with positron emission tomography using nitrogen-13 (N-13) ammonia and fluorine-18 (F-18) deoxyglucose lor assessment of regional perfusion and glucose uptake, respectively. Positron emission tomographic patterns were interpreted as mismatch (perfusion defect with enhanced F-18 deoxyghicose uptake); transmural match (severe concordant reduction or absence of both perfusion and F-18 deoxyglucose uptake) or nontransmural match (mild to moderate concordant reduction of both perfusion and F-18 deoxyglucose uptake).Results. There was no significant correlation (p = 0.14) between the severity of perfusion deficit assessed by positron emission tomography and the collateral grade. The extent of mismatch was unrelated to either the presence or the magnitude of collateral vessels. Conversely, with increasing collateral vessels from grade 1 to 3, the total extent of positron emission tomographic match remained similar, whereas the ratio of transmural to nontransmural match decreased. Myocardial viability was usually present in severely hypokinetic regions (82%). It was lower in akinetic-dyskinetic regions (49%). Of the 64 regions with angiographic collateral vessels, 37 (58%) (95% confidence interval [CI]46% to 70%) showed positron emission tomographic mismatch. In contrast, 7 (50%) of 14 (95% CI 24% to 76%) regions without collateral vessels on angiography exhibited positron emission tomographic mismatch. The presence of angtographically visualized collateral vessels was a sensitive (84%) but not specific (21%) marker of viability.Conclusions. In patients with chronic coronary artery disease, angtographically visualized collateral vessels to asynergc myocardial regions subtended by occluded coronary arteries do not always imply the presence of viable myocardium, suggesting that revascularization may not always provide a functional benefit.     

Comparative effects of nitroglycerin and isosorbide dinitrate on coronary collateral vessels and ischemic myocardium in dogs

To determine the effect of isosorbide dinitrate on ischemic myocardium, this agent was administered to dogs with well developed coronary collateral vessels 8 to 14 weeks after embolization and subsequent occlusion of the left anterior descending coronary artery. After thoracotomy the left coronary artery was cannulated and perfused with blood from the femoral artery. The distal left anterior descending artery was cannulated to monitor peripheral coronary pressure. Regional contractile force in the normal left circumflex and potentially ischemic left anterior descending regions was measured with isometric strain gauge arches sewn to the epicardium. Moderate decreases in coronary perfusion pressure averaging 27 mm Hg produced selective ischemia in the myocardium beyond the site of occlusion of the left anterior descending artery. Under these conditions the average increase in peripheral coronary pressure produced by intracoronary injection of isosorbide dinitrate was 9.0 mm Hg, whereas contractile force in the ischemic region increased by 30 percent. The contractile force was unchanged in the normal regions. Therefore, isosorbide dinitrate can dilate coronary collateral vessels and improve contractile force in ischemic areas. Intracoronary injection of nitroglycerin had similar effects. The durations of responses to isosorbide dinitrate and nitroglycerin were remarkably similar: 6.4 and 6.7 minutes, respectively. Although isosorbide dinitrate can directly dilate coronary collateral vessels, its effects are not longer lasting than those of nitroglycerin.     

肝细胞生长因子对犬急性心肌梗死后左心室重构的影响

目的探讨肝细胞生长因子(hepatocyte growth factor,HGF)对急性心肌梗死后左心室重构的影响。方法将12只杂种犬结扎左冠状动脉前降支,复制急性心肌梗死模型,随机分为2组:对照组和治疗组,每组6只。治疗组于梗死心肌周围注射pc-DNA3-HGF基因1 ml,对照组给予等量的生理盐水。分别于术后1、4、8周进行超声心动图检查,检测心功能、左心室重构指标。术后8周取心肌组织行HE染色及天狼猩红染色,图像分析系统测定Ⅰ、Ⅲ型胶原含量。结果术后4周时,治疗组左心室射血分数(LVEF)明显高于对照组(P<0.05)。8周时,LVEF明显升高,左心室舒张末容积较对照组降低(P<0.05)。对照组组内比较显示左心室后壁厚度显著降低(P=0.04)。HE染色可观察到治疗组梗死心肌周围毛细血管较对照组增多,而对照组瘢痕形成明显。天狼猩红染色显示治疗组Ⅲ型胶原含量高于对照组,Ⅰ/Ⅲ型胶原比例低于对照组(P<0.05)。结论HGF可能通过减少胶原的沉积及促进血管增生,减少心肌坏死及瘢痕形成,从而改善心功能及急性心肌梗死后的左心室重构。     

Contrast echocardiographic mapping of collateralized myocardium in humans before and after coronary angioplasty

Conventional coronary arteriography is able to demonstrate the presence of coronary collateral vessels but cannot delineate the specific region of myocardium to which they supply blood. To test the hypothesis that contrast echocardiography can specifically identify collateralized myocardium, contrast echocardiographic perfusion "maps" were compared in patients with (n = 12) and without (n = 12) angiographic evidence of coronary collateral flow, both before and after coronary angioplasty. Contrast echocardiographic images of the mid-left ventricle in the short-axis view at end-diastole were obtained after separate injections of a sonicated contrast agent into both the right and the left coronary arteries. A computer-based contouring system was used to determine the individual areas of myocardium perfused by each of the two coronary arteries and then to superimpose the images of the two perfusion beds. The resulting area of overlapping perfusion represented myocardium receiving blood flow from both coronary systems and was defined as collateralized myocardium. To normalize for heart size, overlap area was expressed as a percent of total myocardial area, which was the area between endocardium and epicardium in the short-axis view. To adjust for differences in vascular distribution, overlap area was expressed as a percent of the perfusion area of the recipient vessel. In patients with angiographic collateral flow, the recipient vessel was that vessel receiving the collateral flow. In patients without angiographic collateral flow, the right coronary artery was considered the recipient vessel. Overlap area was 1.3 +/- 0.4% of total myocardial area and 6.6 +/- 1.7% of recipient vessel area in patients without angiographic evidence of collateral flow compared with 30.6 +/- 2.5% and 89.2 +/- 6.4%, respectively, in patients with angiographic collateral flow (p less than 0.001 for both). In four patients in whom angiographic collateral flow was abolished by angioplasty, overlap area decreased from 30.3 +/- 5.3% to 6.8 +/- 2.7% of total myocardial area and from 100% to 18.5 +/- 5.4% of recipient vessel area (p less than 0.05 for both). Thus, contrast echocardiography is able to map the specific myocardial territory perfused by coronary collateral flow and document an immediate reduction in perfusion in this territory when collateral flow is abolished by angioplasty.