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1.
Background Cellular cardiomyoplasty by transplantation of various cell types has been investigated as potential treatments for the improvement of cardiac function after myocardial injury. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. AIIogeneic cellular cardiomyoplasty may provide an alternative source of abundant, transplantable, myogenic cells by in vitro manipulation of cardiac fibroblasts using chemicals including 5-azacytidine. This study evaluated cardiomyogenic differentiation of cardiac fibroblasts, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function. Methods Primary cardiac fibroblasts from neonatal rats were treated with 5-azacytidine (10 pmol/L) or control. Treatment of 5-azacytidine caused myogenic differentiation of cultured cardiac fibroblasts, as defined by elongation and fusion into multinucleated myotubes with sarcomeric structures as identified by electron microscopy, and positive immunostaining for cardiac specific proteins, troponin I and 13-myosin heavy chain (13-MHC) and the gap junction protein connexin 43. The myogenic cells (1.0x106) were transplanted into the infarcted myocardium 2 weeks after coronary artery occlusion. Results By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of cardiac-like muscle cells that in the hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins troponin I and 13-MHC. Engrafted cells also expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of culture medium. Heart function was evaluated at 6 weeks after myocardial injury with echocardiographic and hemodynamic measurements. Improvement in cardiac function was seen in the hearts transplanted with the 5-azacytidine-treated cardiac fibroblasts which was absent in the hearts treated with control. Conclusion The 5-azacytidine has a unique capacity to induce myogenesis in cardiac fibroblasts in vitro and transplantation of cardiac-like muscle cells into ventricular scar tissue improves myocardial function.  相似文献   

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Objective To investigate the therapeutic effectiveness of intracoronary implantation of autologous bone marrow mononuclear cells (BM-MNC) in miniswine model of reperfused myocardial infarction.
Methods Sixteen miniswine myocardial ischemic reperfusion injury models made by ligation of the distal one third segment of left anterior descending artery for 90 minutes were randomized into 2 groups. In BM-MNC group (n = 9), (3.54 ± 0.90)× 10^8 BM-MNC were intracoronary injected, and in the control group (n = 7), phosphate buffered saline was injected by the same way. Echocardiographic and hemodynamic results, vessel density, and myocardial infarction size were evaluated and compared before and 4 weeks after cell transplantation.
Results In BM-MNC group, there were no differences between before and 4 weeks after transplantation in aspects of left ventricular ejection fraction (LVEF), interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, or +dp/dtmax. In control group, LVEF, interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, and +dp/dtmax decreased significantly 4 weeks after transplantation (P 〈 0.05). Left ventricular end-diastolic pressure and -dp/dtmax did not change significantly before and after cell transplantation in both groups. Capillary density in BM-MNC group was greater than that in control group [(13.39 ± 6.96)/high power field vs. (3.50 ± 1.90)/high power field, P 〈 0.05]. Infarction area assessed by tetrazolium red staining and the infarction percentage decreased in BM-MNC group compared with those in control group (P 〈 0.05).
Conclusions Transplantation of BM-MNC into myocardium with ischemic reperfusion injury increases capillary density and decreases infarction area. It has significantly beneficial effect on cardiac systolic function rather than on diastolic function.  相似文献   

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The effects of cardiomyocyte grafting on left ventricular (LV) remodeling and function in rats with chronic myocardial infarction were evaluated using high-frequency ultrasound. Chronic myocardial infarction was induced in 50 Wister rats by ligating the left anterior descending artery. They were randomized into two groups: a trial group that received neonatal rat cardiomyocyte trans- plantation (n=25) and a control group which were given intramyocardial injection of culture medium (n=25). The left ventricular (LV) geometry and function were evaluated by high-frequency ultrasound before and 4 weeks after the cell transplantation. After the final evaluation, all rats were sacrificed for histological study. The results showed that 4 weeks after the cell transplantation, as compared with the control group, the LV end-systolic dimension, end-diastolic dimension, end-systolic volume and end-diastolic volume were significantly decreased and the LV anterior wall end-diastolic thickness, LV ejection fraction and fractional shortening were significantly increased in the trial group (P〈0.01). Histological study showed that transplanted neonatal rat cardiomyocytes were found in all host hearts and identified by Brdu staining. It was suggested that transplantation of neonatal rat cardiomyocytes can reverse cardiac remodeling and improve heart function in chronic myocardial infarction rats. High-frequency ultrasound can be used as a reliable technique for the non-invasive evaluation of the effect of cardiomyocyte transplantation.  相似文献   

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To investigate the therapeutic potency of recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in a rabbit myocardial infarction model. Methods: A myocardial infarction was created by the ligation of the major ventricular branch of the left coronary artery in rabbits. After myocardial infarction, the ani-mals were randomly assigned to GM-CSF treatment group, untreated groups and sham-operated group. The rabbits of the treated group were injected into GM-CSF by subcutaneous administration, 10μg/kg/day, once a day for 5 days.The untreated and sham-operated group received a equal saline in the same manner as treated group. Six weeks later echocardiography and haemodynamic assessment were undertaken to assesse cardiac function. The size of the infarct re-gion of the heart were also studied. Restflts: The untreated group exhibited significant higher left ventricle end-diastolic pressure, higher central venous pressure, and with significant lower mean blood pressure, lower peak first derivative of left ventricle pressure (dP/dt) than the sham group. Also, Rabbits in untreated group display significant systolic dys-function shown by the decreased ejection fraction, diastolic dysfunction shown by increasing in the ratio of E wave to A wave (E/A), and display left ventricle enlargement. However, GS-CSF singnificanfly prevented heart dysfunction, left ventricle enlargement, and reduced infarct size in treatment group. Conclusion: Administration GM-CSF after cardiac infarction can improve heart function. These findings indicate the technique may be a novel and simple therapeutic method for ischemic mvocardium.  相似文献   

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Objective To investigate the therapeutic effectiveness of intracoronary implantation of autologous bone marrow mononuclear cells (BM-MNC) in miniswine model of reperfused myocardial infarction. Methods Sixteen miniswine myocardial ischemic reperfusion injury models made by ligation of the distal one third segment of left anterior descending artery for 90 minutes were randomized into 2 groups. In BM-MNC group (n = 9), (3.54±0.90)×108 BM-MNC were intracoronary injected, and in the control group (n = 7), phosphate buffered saline was injected by the same way. Echocardiographic and hemodynamic results, vessel density, and myocardial infarction size were evaluated and compared before and 4 weeks after cell transplantation. Results In BM-MNC group, there were no differences between before and 4 weeks after transplantation in aspects of left ventricular ejection fraction (LVEF), interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, or dp/dtmax. In control group, LVEF, interventricular septal thickness, left ventricular lateral and anterior septal wall thickness, cardiac output, and dp/dtmax decreased significantly 4 weeks after transplantation (P < 0.05). Left ventricular end-diastolic pressure and –dp/dtmax did not change significantly before and after cell transplantation in both groups. Capillary density in BM-MNC group was greater than that in control group [(13.39 ± 6.96)/high power field vs. (3.50 ± 1.90)/high power field, P < 0.05]. Infarction area assessed by tetrazolium red staining and the infarction percentage decreased in BM-MNC group compared with those in control group (P < 0.05). Conclusions Transplantation of BM-MNC into myocardium with ischemic reperfusion injury increases capillary density and decreases infarction area. It has significantly beneficial effect on cardiac systolic function rather than on diastolic function.  相似文献   

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Objective To evaluate the effect of transplanting bone marrow-derived mesenchymal stem cells (BM-MSCs) or adenovirus5-hepatocyte growth factor(Ad5-HGF) via non-infarct-related artery injection in swine myocardial infarction models. Methods BMMSCs were obtained from swine bone marrow and expanded in vitro to a purity of >50%. A myocardial infarction(MI) was created by ligating the distal left anterior descending artery in swine. Either BM-MSCs (5 × 106/ml) or Ad5-HGF (4 × 109 pfu) were transfused via the right coronary artery (non-infarcted artery) four weeks after MI. Gate-controled cardiac perfusion imaging was performed at the end of four and seven weeks after LAD ligation, to evaluate heart function and cardiac perfusion. Morphologic and histologic characteristics of the hearts were also studied. Results (1)The gate-controlled cardiac perfusion imaging showed that the improvement in LVEF was greater in both treatment groups than in control group at the 4th weeks. (2)In both treatment groups, capillary density was significantly higher than that of control group (P < 0.05). ConclusionBM-MSCs or Ad5-HGF transplantation via non-infarcted artery administration can stimulate angiogenesis and improve heart function, but there was no difference in therapeutic efficacy between BM-MSCs and Ad5-HGF.  相似文献   

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Objective To simulate and assess the clinical effect of intracoronary infusion of bone marrow mononuclear cells or peripheral endothelial progenitor cells on myocardial reperfusion injury in mini-swine model. Methods Twenty-three mini-swine with myocardial reperfusion injury were used as designed in the study protocol. About (3.54±0.90)×10^7 bone marrow mononuclear cells (MNC group, n=9) or (1.16± 1.07)× 10^7 endothelial progenitor cells (EPC group, n=7) was infused into the affected coronary segment of the swine. The other mini-swine were infused with phosphate buffered saline as control (n=7). Echocardio- graphy and hemodynamic studies were performed before and 4 weeks after cell infusion. Myocardium infarc- tion size was calculated. Stem cell differentiation was analyzed under a transmission electromicroscope. Results Left ventricular ejection fraction dropped by 0% in EPC group, 2% in MNC group, and 10% in the control group 4 weeks after cell infusion, respectively (P〈0.05). The systolic parameters increased in MNC and EPC groups but decreased in the control group. However, the diastolic parameters demonstrated no significant change in the three groups (P〉0.05). EPC decreased total infarction size more than MNC did (1.60±0.26 cm2 vs. 3.71±1.38 cm2, P〈0.05). Undermature endothelial cells and myocytes were found under transmission electromlcroscope. Conclusions Transplantation of either MNC or EPC may be beneficial to cardiac systolic function, but might not has obvious effect on diastolic function. Intracoronary infusion of EPC might be better than MNC in controlling infarction size. Both MNC and EPC may stimulate angiogenesis, inhibit flbrogenesis, and differentiate into myocardial cells.  相似文献   

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Background Human umbilical cord blood contains an abundance of immature stem/progenitor cells, which may participate in the repair of hearts that have been damaged by myocardial infarction (MI). This study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (hUCBC) transplantation on cardiac function and left ventricular remodeling in rat model of MI. Methods Forty-five male Wistar rats were randomized into three groups: MI or control group (n=15), MI plus cell transplantation (n=15), and sham group (n=15). Acute myocardial infarction (AMI) was established by ligating the left anterior descending artery, thereafter, hUCBC were implanted into the marginal area of infarcted myocardium. In MI/control group, DMEM was injected instead of hUCBC following the same protocol. Left ventricular function assessment was carried out by echocardiography and invasive hemodynamic measurements one month post MI. All rats were sacrificed for histological and immunochemical examinations. Results The transplanted hUCBC survived and engaged in the process of myocardial repair in the host heart. Echocardiography demonstrated that left ventricular function improved significantly in the rats that underwent cell transplantation. Hemodynamic studies found a significantly decreased left ventricular end-diastolic pressure (LVEDP) [(21.08±8.10) mmHg vs (30.82±9.59) mmHg, P&lt;0.05], increase in +dp/dt(max) [(4.29±1.27) mmHg/ms vs (3.24±0.75) mmHg/ms, P&lt;0.05), and increase in -dp/dt(max) [(3.71±0.79) mmHg/ms vs (3.00±0.49) mmHg/ms, P&lt;0.05] among MI group with hUCBC transplantation when compared with MI/control group. Masson’s trichrome staining revealed that the collagen density in the left ventricle was significantly lower in rats of transplantation group than that in the MI control groups [(6.33±2.69)% vs (11.10±3.75)%, P&lt; 0.01]. Based on immunostaining of α-actin, the numbers of microvessels were significantly (P&lt;0.01) increased at the boundary of infarction site. Similarly higher mRNA expression of vascular endothelial growth factor (VEGF) 164 and VEGF188 were found at 7- and 28-day post cell transplantation in MI group with hUCBC transplantation when compared with MI/ control group.Conclusions Transplanted hUCBC can survive in host myocardium without immunorejection, significantly improve left ventricular remodeling after AMI and promote a higher level of angiogenesis in the infarct zones. All these factors beneficially affect cardiac repair in the setting of MI. Therefore human umbilical cord blood may be potential source for cell-based therapy for AMI.  相似文献   

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目的对比研究棕色脂肪干细胞(BADSCs)与白色脂肪干细胞(ADSCs)治疗急性心肌梗死大鼠的效果。方法采用酶消化法分别分离大鼠腹股沟脂肪组织及肩胛骨下脂肪组织,获得ADSCs与BADSCs,并进行流式分析与多谱系分化鉴定。30只雄性SD大鼠随机分为PBS对照组、ADSCs移植组及BADSCs移植组,建立急性心肌梗死模型,将各组对应细胞直接注入大鼠心肌梗死边缘区。移植后4周进行心功能检测并利用组织学检测移植细胞的体内分化与血管化作用。结果术后4周,与PBS对照组相比,ADSCs以及BADSCs移植组大鼠心功能均显著提高(P〈0.05),且纤维化程度显著减弱(P〈0.05)。免疫荧光结果表明,移植的BADSCs成心肌分化数量显著高于ADSCs。免疫组化结果显示,ADSCs移植组以及BADSCs移植组大鼠心肌梗死区血管密度均较PBS对照组显著增加(P〈0.05),ADSCs移植组血管密度显著高于BADSCs移植组(P〈0.05)。结论不同来源脂肪干细胞移植均具有改善心肌梗死患者心功能的作用,虽然BADSCs体内促血管化作用不如ADSCs,但其具有明显的心肌分化能力,可有效改善心脏功能。  相似文献   

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目的探讨脂肪来源的间充质干细胞(ADSCs)对大鼠急性心肌梗死(AMI)后心功能的影响。方法结扎SD大鼠左冠状动脉前降支制备心肌梗死模型。同种异体ADSCs体外分离、培养、纯化、扩增,在大鼠AMI区域周围进行心外膜下移植。将24只大鼠随机分为3组,每组8只:A组为AMI模型组,只给予前降支结扎;B组为细胞培养基(DMEM)移植组,结扎后心外膜注射DMEM;C组为ADSCs治疗组,结扎前降支后接受ADSCs移植治疗。术后7 d、28 d各组大鼠行心脏超声检测左室射血分数(LVEF)、左室短轴缩短率(FS),28 d超声检测后行血流动力学测量左室收缩压、左室舒张末压、左心室压力最大变化速率,评价ADSCs移植对AMI后大鼠心功能的影响;心脏组织行TTC染色,观察AMI面积。结果与AMI模型组比较,ADSCs治疗组的LVEF、FS及血流动力学指标明显提高(P0.01)。TTC染色观察心肌梗死面积,ADSCs治疗组心肌梗死面积明显减小(P0.01)。结论 ADSCs可减少AMI的面积,改善心功能。  相似文献   

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OBJECTIVE: To test the effect of autologus marrow stromal cells (MSCs) transplantation combined with application of granulocyte colony stimulating factor (G-CSF) on the function of ischemic hearts in vivo. METHODS: Acute myocardial infarction was induced in rabbits by occlusion of the left anterior descending artery, and autologous MSCs labeled with BrdU in vitro was introduced in the infarct area of the same donor rabbit. G-CSF was administered by subcutaneous injection for 5 consecutive days. Four weeks later, the transplanted MSCs were detected by laser scanning confocal microscopy and the cardiac function of the rabbits was examined by echocardiogram and multichannel physiological recorder. The myocardial infarct size was measured on the mid-transverse sections stained with Masson's trichrome. RESULTS: Four weeks after transplantation, the MSCs were found to undergo myogenic differentiation with expressions of alpha-sarcomeric actin and connexin 43 in the intercalated disk. MSC transplantation in combination with G-CSF administration improved the left ventricular contractility and markedly reduced myocardial infarct size as compared with cell transplantation without G-CSF. CONCLUSION: Application of G-CSF following autologous MSC transplantation may represent a promising therapeutic strategy for ischemic heart disease.  相似文献   

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骨髓干细胞动员与移植治疗心肌梗死的比较   总被引:1,自引:0,他引:1  
目的比较骨髓干细胞动员与骨髓单个核细胞移植对兔心肌梗塞的治疗作用,探讨更有效、更适用的干细胞治疗心肌梗塞的方法.方法将30支新西兰白兔采用结扎前降支的方法制作心肌梗塞模型,随机分为动员组、移植组和对照组,动员组(n=10)心梗后3h开始皮下注射粒细胞集落刺激因子(G-CSF)30μg/(kg·d),连续使用5 d,第5天抽取静脉血约10mL,分离单个核细胞(mononudear cells,MNCs)用5-溴脱氧尿嘧啶核苷(bromodeoxyuridine,Brdu)标记后,经静脉注入动物体内.移植组(n=10)心梗后7~10 d,抽取骨髓3~5mL,分离MNCs用Brdu标记,然后开胸将细胞移植至梗死区,对照组(n=10)不采取任何治疗措施.心梗后1周及5周采用超声心动图(UCG)检查了解心脏功能变化,5周时作血液动力学测定,取心脏作免疫组织化学鉴定.结果心梗后5周,动员组左室射血分数(EF)与1周时相比明显增加,移植组无变化,对照组显著下降.5周时动员组及移植组左室舒张末压(LVEDP)、+dp/dtmax和-dp/dtmax与对照组相比均有显著变化.动员组及移植组在心肌梗死区均发现有Brdu标记的阳性细胞,两组梗死区血管密度明显高于对照组,但均未发现有新生的平滑肌细胞及心肌细胞.结论骨髓干细胞动员治疗心肌梗死,能通过促进梗死区血管新生,明显改善心脏功能,骨髓单个核细胞移植可避免心功能的恶化,但在改善心功能方面的作用有限,骨髓干细胞动员可能为心肌梗塞的治疗提供一种更适用的无创性的手段.  相似文献   

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 目的 探讨骨髓单个核细胞植入对心肌梗死后心脏功能的影响。 方法 以冷冻损伤的方法建立新西兰种家兔心肌梗死模型,分为骨髓单个核细胞组(mononuclear bone marrow cells,MN-BMCs组)和对照组,各8只。4周后, MN-BMCs组中将提取分离的MN-BMCs,植入心肌梗死及其边缘区,对照组于心肌梗死及其边缘区注射相应体积的IMDM完全培养液。以超声心动图分析细胞植入前后心脏功能改善情况。 结果 MN-BMCs植入心肌梗死及其边缘区可以改善局部及整体心脏功能:细胞移植4周后两组之间比较,MN-BMCs组局部心脏功能明显优于对照组,表现为MN-BMCs组比对照组心肌梗死区室壁厚度增加,(4.81±0.55)mm vs 3.94±0.54)mm,P<0.05;收缩期和舒张期心肌梗死区室壁运动速度明显增加,分别为(8.20±0.77)cm/s vs 7.00±0.56)cm/s,P<0.05,(8.51±0.93) cm/s vs (6.75 ±0.57)cm/s,P<0.05。细胞移植4周后,MN-BMCs组整体心脏功能亦优于对照组,表现为MN-BMCs组比对照组心腔减小,LVDD分别为 (14.89±1.36)mm vs (16.24±1.31)mm,P<0.05,LVSD分别为(10.48±1.32)mm vs (12.29±1.48)mm,P<0.05;MN-BMCs组左心室收缩功能明显改善,左室射血分数及缩短分数提高,LVEF分别为(65.25±5.73)% vs (57.00±5.81)%,P<0.05,LVFS分别为 (30.25±3.73)% vs (24.88±3.95)%,P<0.05。 结论 骨髓单个核细胞植入心肌梗死及其边缘区可以改善心肌梗死后心脏功能。  相似文献   

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目的:观察干细胞移植在急性心肌梗死( AMI )后心衰患者中的临床疗效。方法选择2006年8月-2010年6月收治的急性ST段抬高心肌梗死(STEMI)合并心衰,Killip分级Ⅱ级及Ⅱ级以上,常规药物治疗无效,左室射血分数(LVEF)<45%的患者,共30例。将入选患者随机分成两组,其中干细胞移植组19例,对照组11例。移植组于PCI术后5 d行干细胞移植术,用冠脉造影注射法,采集经粒细胞集落刺激因子动员5 d的外周血干细胞(PBSC)悬液,经流式细胞仪分离计数CD+34细胞(大约1×1010~1×1011/L),注入梗死相关血管。对照组以同样方法于冠脉内注射等量生理盐水。观察移植组术前、术后6个月、2年、最长5年以及对照组常规治疗6个月、2年、5年的心功能情况。比较移植前后左室射血分数( LVEF)和左室舒张末期容积( LVDd)数值。结果移植组干细胞移植后6个月左室射血分数为(42.4±5.6)%,明显高于移植前的(38.6±5.4)%及对照组(38.7±5.1)%,P<0.05。移植组干细胞移植后6个月舒张末期容量(内径)(58.50±4.6)mm,明显小于移植前的(60.00±7.5)mm, P<0.05。结论经皮冠状动脉内自体外周血干细胞移植能明显改善急性心肌梗死患者的左室功能,减小左室容量,阻止或延缓左室重构,且安全有效。  相似文献   

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目的:观察静脉移植骨髓间充质干细胞(MSC)联合促红素(EPO)治疗心肌梗死的可能性。方法:大鼠MSC培养后,制备成悬液备用。40只Lewis大鼠用异丙肾上腺素(ISO)制作急性心肌梗死模型,随机分为4组:A.MSC加EPO治疗组(n=10);B.MSC治疗组(n=10);C.EPO治疗组(n=10);D.心肌梗死对照组(n=10)。4周后,观察大鼠的心功能、血流动力学变化。结果:与对照组相比,MSC加EPO组、MSC组和EPO组的心功能明显改善,左室腔明显缩小(P<0.05),梗死面积减少;其中MSC加EPO组较MSC组和EPO组的心功能好(P<0.05)。结论:骨髓MSC联合EPO治疗大鼠急性心肌梗死取得了良好的效果,比单用效果好。  相似文献   

18.
目的观察附加丹参注射液(SM)和1,6-二磷酸果糖(FDP)的St.Thomas液持续低温微量灌注离体大鼠心脏的保护作用.方法SD大鼠24只,随机分为4组(n=6):对照组、SM组、FDP组、SM+FDP组.离体大鼠心脏用冰冷的St.Thomas液停搏后,用Langendorff方式灌注K-H液30min,测定心功能:左心室压力变化速率最大值(±dP/dtmax)、左心室发展压(LVDP)、心率(HR)和冠脉流量(CF),然后分别用St.Thomas液、St.Thomas液+SM、St.Thomas液+FDP、St.Thomas液+SM+FDP停搏心脏,并在4℃条件下持续灌注(20μL/min)保存6h,再以Langendorff方式复灌30min,再次测定心功能指标,最后分析持续灌注保存液中乳酸脱氢酶(LDH)、肌酸激酶(CK)活性以及心脏含水量.结果SM组、FDP组和SM+FDP组的+dP/dtmax恢复率和FDP组的LVDP恢复率均明显高于对照组;SM组、FDP组、SM+FDP组的LDH活性和FDP组、SM+FDP组的CK活性均明显低于对照组(P〈0.05);在心功能和酶学测定结果中,SM、FDP分别单用与两者合用相比较无明显差异(P〉0.05).结论应用低温持续微量灌注保存方法,在St.Thomas液中单独添加SM或FDP均可改善心脏保存效果,两者伍用效果与单用比较无明显差别.  相似文献   

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