Sample records for cardiomyoplasty

  1. Cellular Cardiomyoplasty: Clinical Application

    Chachques, J. (J.); Acar, C; J. Herreros; Trainini, J. (Jorge); Prosper, F.; D’Attellis, N. (N.); Fabiani, J. N.; Carpentier, A


    Myocardial regeneration can be induced with the implantation of a variety of myogenic and angiogenic cell types. More than 150 patients have been treated with cellular cardiomyoplasty worldwide, 18 patients have been treated by our group. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit postischemic remodelling, and restore regional myocardial contractility. Techniques for skeletal myoblasts culture and ex vivo expansion using auto...

  2. Cellular cardiomyoplasty: what have we learned?

    Kao, Race L; Browder, William; Li, Chuanfu


    Restoring blood flow, improving perfusion, reducing clinical symptoms, and augmenting ventricular function are the goals after acute myocardial infarction. Other than cardiac transplantation, no standard clinical procedure is available to restore damaged myocardium. Since we first reported cellular cardiomyoplasty in 1989, successful outcomes have been confirmed by experimental and clinical studies, but definitive long-term efficacy requires large-scale placebo-controlled double-blind randomized trials. On meta-analysis, stem cell-treated groups had significantly improved left ventricular ejection fraction, reduced infarct scar size, and decreased left ventricular end-systolic volume. Fewer myocardial infarctions, deaths, readmissions for heart failure, and repeat revascularizations were additional benefits. Encouraging clinical findings have been reported using satellite or bone marrow stem cells, but understanding of the benefit mechanisms demands additional studies. Adult mammalian ventricular myocardium lacks adequate regeneration capability, and cellular cardiomyoplasty offers a new way to overcome this; the poor retention and engraftment rate and high apoptotic rate of the implanted stem cells limit outcomes. The ideal type and number of cells, optimal timing of cell therapy, and ideal cell delivery method depend on determining the beneficial mechanisms. Cellular cardiomyoplasty has progressed rapidly in the last decade. A critical review may help us to better plan the future direction. PMID:19515892

  3. Cellular cardiomyoplasty A preliminary clinical report

    Background: Cellular cardiomyoplasty is the method of transplanting myogenic cells into injured myocardium to restore the lost heart muscle cells and to improve ventricular function. Method: Three patients, all with a history of coronary heart disease, underwent coronary artery bypass grafting and implantation of autologous satellite cells. A muscle biopsy of 2-4 g from the right vastus lateralis muscle was obtained for satellite cell (myogenic stem cell from skeletal muscle) isolation and proliferation before implanted into the donor's heart. The cells were suspended in serum-free medium and injected into 30-40 sites at and around the ischemic areas just before reversing the hypothermic cardioplegia to eliminate arrhythmia and to improve retention. After recovery, each patient was maintained at the intensive care unit for 3-4 days with ECG monitoring before transferring to the patient floor. Results: All patients survived the procedure with an uneventful recovery and were discharged from the hospital. At 3-4 months follow-up examination, increased left ventricular ejection fraction of 11% (35-46%), 5.4% (40-45.4%) and 1% (40-41%) and decreased left ventricular diastolic diameter of 4, 2 and 9 mm were observed for the patients, respectively. Arrhythmia was not detected during the follow-up evaluation by ECG. Improved perfusion (99mTC-MIBI) and increased metabolic activity (18F-deoxyglucose) were found at the sites of satellite cell implantation. Significant increase of wall thickness and movement at the areas of cell injection was also observed using 2D-echo. Conclusion: Cellular cardiomyoplasty using autologous satellite cells is a safe procedure with encouraging beneficial outcomes in patients

  4. Cardiomioplastia: novo gerador da Biotronic Cardiomyoplasty: a new Biotronic generator

    Domingo M Braile


    ,0%, referentes a seguimento médio de 14,2 meses, refletem que a cardiomioplastia pode ser efetiva na assistência do ventrículo esquerdo. A escolha do paciente parece ser a chave para o bom resultado operatório a curto e longo prazos.In the cardiomyoplasty, the contraction of the skeleton muscle, undergone electric stimulation on the dilated ventricle wall, increases the ventricle function, which is dependent of the heart and the base disease previous conditions. One of the main problems which interferes with the sucess of the cardiac muscle replacement is the myocardial synchronic stimulation and the skeleton muscle. The stimulation of this muscle in long-term has been possible because of the special electrodes associated with the sequential progressive stimulation, adjusting it to the cardiac function, through the gradual transformation of glicolitic fibers exposed to fatigue in highly resistant slow oxidizers. The pulse generator Myos (Biotronik has been used in our center for electrical stimulation of the latissimus dorsalis in synchronization with the myocardium. This electronic circuit and lithium battery type of cardiomyostimulator stores a stimulation program responsible for different operational modes, adapted by acomputer program. In order to program the cardiomyostimulator, the moment of the pulse synchronization with the aortic valve opening is extremely important. The high velocity M mode is utilized to evaluate the synchronism. The cardiomyoplasty clinical evaluation is based on the results obtained from 32 patients at 22 ti 72 years old (average=46.2 years most of patients (72% presented dilated myocardiopathy due to undetermined cause, 24% of chagasic origin, 3% virus and 3% due to peripartum. Hospital and late mortality rate were both 12.5% and 3.1% and 3.7% respectively, excluding the chagasic patients. The actuarial survival was 81.3 + - 0.22% after 6 years and 94.4 + - 0.1 % after 5 years, withdrawing the chagasic patients. The average indexes of systolic

  5. Serial assessment of rest and exercise left ventricular ejection fraction (LVEF) post-cardiomyoplasty

    Full text: Previous studies have shown that the patient's functional class as well as overall quality of life significantly improved with cardiomyoplasty (CM). However, results of objective measurement of left ventricular function remains controversial. The aim of this study was to determine whether there is objective improvement in left ventricular function following cardiomyoplasty. Method: 26 patients with class III New York Heart Association (NYHA) heart failure (mean age 58±7 years) were randomised to cardiomyoplasty (n=12) or control (n=14). Aetiology was idiopathic dilated cardiomyopathy in 85% and ischaemic heart disease in 15%. Groups were well matched at baseline with respect to sex, age, aetiology, NYHA functional class and baseline ejection fraction. Symptom-limited maximal bicycle exercise tests were performed pre-operatively and at 3, 6, 12, 24, and 36 months post-operatively. Resting LVEF: Although some increase in resting LVEF was noted in each group, this increase was not statistically significant (p> 0.05) when compared to baseline. Exercise LVEF: Significant increase in LVEF at peak exercise was noted at six months (p=0.04), 12 months (p=0.03) and 24 months (p=0.01) in the CM group but not in the control group or in the CM group at three months. In conclusion the significant increase in LVEF with exercise in the CM group contributes to the symptomatic improvement seen in the majority of CM patients, and strongly supports the hypothesis of direct systolic assist as one of the mechanisms. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  6. Cardiac supporting device using artificial rubber muscle: preliminary study to active dynamic cardiomyoplasty.

    Saito, Yoshiaki; Suzuki, Yasuyuki; Goto, Takeshi; Daitoku, Kazuyuki; Minakawa, Masahito; Fukuda, Ikuo


    Dynamic cardiomyoplasty is a surgical treatment that utilizes the patient's skeletal muscle to support circulation. To overcome the limitations of autologous skeletal muscles in dynamic cardiomyoplasty, we studied the use of a wrapped-type cardiac supporting device using pneumatic muscles. Four straight rubber muscles (Fluidic Muscle, FESTO, Esslingen, Germany) were used and connected to pressure sensors, solenoid valves, a controller and an air compressor. The driving force was compressed air. A proportional-integral-derivative system was employed to control the device movement. An overflow-type mock circulation system was used to analyze the power and the controllability of this new device. The device worked powerfully with pumped flow against afterload of 88 mmHg, and the beating rate and contraction/dilatation time were properly controlled using simple software. Maximum pressure inside the ventricle and maximum output were 187 mmHg and 546.5 ml/min, respectively, in the setting of 50 beats per minute, a contraction/dilatation ratio of 1:2, a preload of 18 mmHg, and an afterload of 88 mmHg. By changing proportional gain, contraction speed could be modulated. This study showed the efficacy and feasibility of a pneumatic muscle for use in a cardiac supporting device. PMID:26253252

  7. Myocardial perfusion and left ventricular function in long-term follow-up and prognosis of electrostimulation cardiomyoplasty

    Background: Twenty two patients with congestive cardiac failure treated surgically by dynamic cardiomyoplasty (CMP) with m. latissimus dorsi were examined. Myocardial perfusion was assessed with 199TlCl scintigraphy combined with dipyridamole stress-test. In order to obtain direct evidence of myocardial perfusion from muscular flap we also injected a bolus of 99mTc into a. thoracodorsalis, with simultaneous blood sampling from coronary sinus. Haemodynamic parameters were assessed using radionuclide angiography. METHODS In a year of follow-up all the patients were assigned to one of two groups: eleven patients demonstrated improvement in clinical status (first group) and in another group comprising eleven persons no positive effect or deterioration were obvious (second group). The patients of the first group before operation revealed two times less persistent defect size than patients of the second group. Analysis of integral index of persistent defect revealed more expressive differences between groups. Before the surgical treatment the patients with improvement in clinical status after cardiomyoplasty demonstrated greater size of reversible defect in comparison with patients of the second group. In the second group coronary fraction of thallium accumulation was 1.4 times higher in comparison to the first group, as the result of myocardial hypertrophy in patients with bad prognosis. There were no significant differences between the two groups in Il/m level before cardiomyoplasty. Before the surgical treatment the patients with improvement in clinical status after cardiomyoplasty demonstrated greater ejection fraction in comparison with patients of the second group. RESULTS Cardiomyoplasty led to a decrease in the mean size of reversible defects due to indirect revascularisation. This hypothesis was testified to by the fact that in patients after cardiomyoplasty nuclide appeared in coronary sinus at 10-12 seconds after injection into artery thoracodorsalis through

  8. Resultados da cardiomioplastia no tratamento da cardiomiopatia dilatada Cardiomyoplasty results in the treatment of dilated cardiomyopathy

    Luiz Felipe P Moreira


    Full Text Available A cardiomioplastia tem sido proposta como uma alternativa ao transplante cardíaco no tratamento das cardiomiopatias isquémicas ou dilatadas. No período de maio de 1988 a outubro de 1990, 16 pacientes portadores de cardiomiopatia dilatada foram submetidos à cardiomioplastia no Instituto do Coração. Dez pacientes estavam em classe funcional III e seis em classe IV. Não houve óbitos no período de pós-operatório imediato. O tempo médio de seguimento foi de 16,9 ± 2,5 meses e a sobrevida atuarial foi 74% no 1º ano e 64,8% no 2º ano após a cardiomioplastia, sendo influenciada pela má evolução dos pacientes operados com diâmetro de ventrículo esquerdo maior do que 80 mm. Esses valores foram superiores, contudo, à sobrevida de um e dois anos de 39,5 e 29,6%, respectivamente, apresentada pelo grupo controle de 20 pacientes mantidos clinicamente (p = 0,06. Cinco dos 11 pacientes em seguimento após a cardiomioplastia, retornaram à classe funcional I e seis estão em classe II. Aos seis meses de pós-operatório, foi documentada a elevação da fração de ejeção do ventrículo esquerdo de 20,1 ± 3,8 para 26 ± 7,8% pelo estudo radioisotópico (p Dynamic cardiomyplasty has been proposed as an alternative surgical treatment for severe cardiomyopathies. From May 1988 to October 1990, dynamic cardiomyoplasty was performed in 16 patients with dilated or chagasic cardiomyopathy at the Heart Institute. Ten patients were in New York Heart Association (NYHA Class III and six in Class IV. There were no operative deaths. During a men follow-up of 16.9 ± 2.5 months, the actuarial survival was 74% at 1 year and 64.8% at 2 years of follow-up. This survival was influenced by the worse evolution of patients with left ventricular internal diameter more than 80 mm. These results were, however, better than the survival of 39.5 and 29.6%, presented at the same periods, respectively, by 20 patients maintained under medical therapy. Five of the 11

  9. Evaluation of passive cardiomyoplasty using left- and right-ventricular volume measurements by EBCT and MRI in patients with chronic congestive heart failure

    Purpose: To evaluate the efficacy of passive cardiomyoplasty with the determination of biventricular volumes, global systolic function as well as left-ventricular muscle mass. Materials and Methods: In 19 patients with congestive heart failure of idiopathic or ischemic origin, a polyester mesh-graft was implanted around both ventricles for stabilization and functional support. Before and three months after surgery, 15 patients underwent EBCT and 4 patients with impaired renal function underwent MRI, for the evaluation of the volume and ejection fraction of both ventricles. Results: EBCT demonstrated a decrease from 385 to 310 ml in LV-EDV, from 312 to 242 ml in LV-ESV, from 209 to 160 ml in RV-EDV and from 149 to 87 ml in RV-ESV, and an increase from 20 to 26% in LV-EF and from 37 to 50% in RV-EF as well as a reduction of LV-MM from 300 to 274 g (p < 0.05 each). Similar results were obtained by MRI. Conclusion: Following passive cardiomyoplasty, EBCT and MRI revealed an improvement of the global systolic function as well as a reduction of biventricular volumes and left-ventricular muscle mass. (orig.)

  10. Actual problems of cellular cardiomyoplasty

    Bulat Kaupov


    Full Text Available The paper provides review of cellular technologies used incardiology, describes types of cellular preparations depending onsources of cells and types of compounding cells. The generalmechanisms of therapies with stem cells applications are described.Use of cellular preparations for treatment of cardiovascular diseasesand is improvement of the forecast at patients with heartinsufficiency of various genesis is considered as alternative topractice with organ transplantations. Efforts of biotechnologicallaboratories are directed on search of optimum population of cellsfor application in cardiology and studying of mechanisms andfactors regulating function of cardiac stem cells.

  11. Risk factors of mortality in nine years of follow-up after dynamic cardiomyoplasty Fatores determinantes de mortalidade em nove anos de seguimento pós cardiomioplastia dinâmica

    Anderson Benício


    Full Text Available PURPOSE: To retrospectively evaluate the survival rate of patients that underwent dynamic cardiomyoplasty, determining the influence of pre-, intra- and post-operative factors and the evolution of left ventricle ejection fraction according to the stimulation mode. METHOD: Forty-three patients that underwent dynamic cardiomyoplasty between May 1988 and September 1997 were analyzed. Functional class III was predominant (81.4%. The mean left ventricle ejection fraction was 19.37 ± 3.48%. Hospital death was 2.2% and 39 patients who completed the conditioning period had a mean follow up of 46 ± 26 months. Twenty-eight patients were predominantly maintained under stimulation mode 1:1 and 11 under 1:2 stimulation mode. RESULTS: Survival rate at nine years of follow up was 9%. The causes of death were progression of the heart failure and sudden cardiac death. Functional class, the pulmonary vascular-resistance index and stimulation mode were identified as risk factors. The maintenance of the increase of the left ventricle ejection fraction when compared to the preoperative values was more consistent during the studied period when the graft was stimulated in the 1:2 mode. CONCLUSION: Late results of dynamic cardiomyoplasty are limited by the high incidence of deaths by progression of the heart failure and sudden cardiac death. Survival rate is influenced by the preoperative clinical condition and by the stimulation mode. Muscle graft performance is higher at late follow up with the 1:2 stimulation mode.OBJETIVO: Analisar, retrospectivamente, a sobrevivência dos pacientes submetidos a cardiomioplastia dinâmica, determinando a influência de fatores pré, intra e pós-operatório e o comportamento da fração de ejeção conforme o modo de estimulação. MÉTODO: Foram analisados 43 pacientes submetidos a cardiomioplastia dinâmica, no período de maio de 1988 a setembro de 1997. A classe funcional III foi predominante (81,4%. A fração de ejeção m

  12. Bases experimentais da utilização da cardiomioplastia no tratamento da insuficiência miocárdica Experimental basis of cardiomyoplasty utilization in the treatment of myocardial insufficiency

    Luiz Felipe P Moreira


    Full Text Available A cardiomioplastia é uma técnica que utiliza enxertos musculares esqueléticos, estimulados síncronamente ao coração, para substituir, ou envolver o miocárdio. O objetivo deste trabalho foi analisar as características contrateis e a resistência à fadiga do músculo grande dorsal normal e estimulado cronicamente, bem como avaliar a eficiência da cardiomioplastia como método de suporte circulatório. Treze cães foram estudados, após condicionamento elétrico do músculo grande dorsal esquerdo, por período de 6 semanas. Sete deles foram submetidos a medida isométrica da força exercida pelos músculos condicionados e pelos controles contralaterais e a estudo morfológico. Os parâmetros ideais de estimulação foram semelhantes para os músculos normais e os condicionados. Os músculos condicionados, constituídos, predominantemente, de fibras de ação lenta, apresentaram uma força de amplitude menor (-27% e um tempo de contração mais longo (+32%. Por outro lado, as curvas de fadiga dos músculos normais, constituídos de fibras mistas, mostraram a queda inicial da força de contração e valores estáveis, após 30 minutos, inversamente proporcionais à freqüência das contrações, resultando em um mesmo índice tensão-tempo (18 ± 2 kgF. seg/min. Já os músculos condicionados apresentaram um desempenho estável nas mesmas freqüências, mantendo um índice tensão-tempo elevado (68 ± 6 kgF. reg/min. Os outros 6 animais foram submetidos a cardiomioplastia, sendo estudados hemodinâmica e ecocardiograficamente, após a indução de disfunção miocárdica. Com a estimulação síncrona do músculo esquelético, observou-se a elevação do índice cardíaco em 36 ± 4% (pBeneficial effects of cardiomyoplasty have been documented and the use of this technique in the treatment of dilated cardiomyopathy have been suggested. This study was undertaken to evaluate the contracting and fatigue characteristics of normal and

  13. Evolução clínica e comportamento da função ventricular no pós-operatório tardio da cardiomioplastia Clinical and ventricular function in the late follow-up of dynamic cardiomyoplasty

    Luiz Felipe P Moreira


    Full Text Available A cardiomioplastia tem sido proposta, como uma alternativa ao transplante cardíaco, no tratamento de pacientes com insuficiência miocárdica em fase avançada. O objetivo deste trabalho é estudar a evolução clínica e o comportamento da função ventricular no pós-operatório tardio desse procedimento em 34 pacientes portadores de cardiomiopatia dilatada, que foram operados no período de maio de 1988 a setembro de 1994. Vinte e sete pacientes estavam em classe funcional III e 7 pacientes em classe IV no preoperatorio, apesar do uso de terapêutica clínica otimizada. A mortalidade hospitalar foi de 2,9% e 1 paciente que evoluiu em choque cardiogênico foi submetido a transplante cardíaco 42 dias após a cardiomioplastia. O tempo de seguimento pós-operatório variou entre 2 e 73 meses, com média de 27,4 meses. Aos 6 meses de pós-operatório, 12 pacientes estavam em classe funcional 1,15 pacientes em classe 11 e 3 pacientes em classe III (p=0,001 em relação ao pré-operatório. Quatorze pacientes faleceram até 5 anos de pós-operatório e os índices de sobrevida foram 84,7% em 1 ano, 67,7% em 2 anos e 39,6% aos 5 anos de seguimento, sendo que, em 9 pacientes, os óbitos ocorreram por progressão da insuficiência cardíaca, e 5 pacientes faleceram subitamente. A análise de regressão de Gox mostrou que a mortalidade nos pacientes operados em classe funcional IV foi 5,5 vezes maior do que nos pacientes operados em classe III (p=0,006, cuja sobrevida foi de 52,7% aos 5 anos de pós-operatório. O estudo sistemático da função ventricular através da angiografia com radioisótopos, da ecocardiografia com Doppler e do cateterismo cardíaco direito documentou a melhora da fração de ejeção do ventrículo esquerdo (V E de 19,8 ± 3 para 23,9 ± 7,2% (pDynamic cardiomyoplasty has been proposed as an alternative to heart transplantation in the treatment of severe cardiomyopathies. In this investigation, its results were investigated

  14. Evaluation of passive cardiomyoplasty using left- and right-ventricular volume measurements by EBCT and MRI in patients with chronic congestive heart failure; Evaluierung der passiven Kardiomyoplastie mittels links- und rechtsventrikulaerer EBCT- und MRT-Volumetrie bei Patienten mit chronischer Herzinsuffizienz

    Lembcke, A.; Enzweiler, C.N.H.; Wiese, T.H.; Kivelitz, D.E.; Rogalla, P.; Hamm, B. [Inst. fuer Radiologie, Universitaetsklinikum Charite, Campus Charite Mitte, Humboldt Univ. zu Berlin (Germany); Hotz, H.; Dushe, S.; Konertz, W. [Klinik fuer Kardiovaskulaere Chirurgie, Universitaetsklinikum Charite, Campus Charite Mitte, Humboldt Univ. zu Berlin (Germany)


    Purpose: To evaluate the efficacy of passive cardiomyoplasty with the determination of biventricular volumes, global systolic function as well as left-ventricular muscle mass. Materials and Methods: In 19 patients with congestive heart failure of idiopathic or ischemic origin, a polyester mesh-graft was implanted around both ventricles for stabilization and functional support. Before and three months after surgery, 15 patients underwent EBCT and 4 patients with impaired renal function underwent MRI, for the evaluation of the volume and ejection fraction of both ventricles. Results: EBCT demonstrated a decrease from 385 to 310 ml in LV-EDV, from 312 to 242 ml in LV-ESV, from 209 to 160 ml in RV-EDV and from 149 to 87 ml in RV-ESV, and an increase from 20 to 26% in LV-EF and from 37 to 50% in RV-EF as well as a reduction of LV-MM from 300 to 274 g (p < 0.05 each). Similar results were obtained by MRI. Conclusion: Following passive cardiomyoplasty, EBCT and MRI revealed an improvement of the global systolic function as well as a reduction of biventricular volumes and left-ventricular muscle mass. (orig.) [German] Ziel: Evaluierung des Therapieerfolges der passiven Kardiomyoplastie durch Bestimmung der biventrikulaeren Volumina und global systolischen Funktion sowie der linksventrikulaeren Muskelmasse. Methoden: Bei 19 Patienten mit idiopathisch und ischaemisch bedingter Herzinsuffizienz erfolgte die Implantation eines Polyesternetzes um die Ventrikel zu deren Stabilisierung und funktioneller Unterstuetzung. Praeoperativ sowie drei Monate postoperativ wurden bei 15 Patienten durch EBCT und bei 4 Patienten mit eingeschraenkter Nierenfunktion durch MRT die Volumina und Ejektionsfraktion beider Ventrikel sowie die linksventrikulaere Muskelmasse bestimmt. Ergebnisse: Die EBCT zeigte eine Abnahme des LV-EDV von 385 auf 310 ml, des LV-ESV von 312 auf 242 ml, des RV-EDV von 209 auf 160 ml und des RV-ESV von 149 auf 87 ml, eine Zunahme der LV-EF von 20 auf 26% und der RV


    Lukash, L.


    The review article is devoted to cellular cardiomyoplasty as a novel technology of treatment of cardiac insufficiency. The experiments on animals and the first clinical trials have shown the possibility to improve the contractile function of diseased heart after transplantation of different types of donor cells: cardiomyocytes, bone marrow enriched by hematopoietic stem cells and mesenchymal stem cells. The problems of cellular cardiomyoplasty are discussed.

  16. Cellular cardiomyoplasty with bone marrow mesenchymal stem cells and ramipril improves cardiac performance induced by infarct in rabbits%骨髓间充质干细胞移植和雷米普利对兔心肌梗死后心功能影响的对照研究

    陈建昌; 蒋文平; 刘志华; 程绪杰; 李红霞


    目的探讨诱导分化后的骨髓间充质干细胞(MSC)移植和血管紧张素转换酶抑制剂(ACEI)雷米普利在改善兔心肌梗死(MI)后的心功能方面是否具有协同作用.方法40只经结扎冠状动脉前降支形成MI的兔随机分为四组,两组不予雷米普利,MI后2周心肌内注射培养基(1组)或诱导分化后的MSC(2组);另两组MI后即通过饮水途经给予雷米普利1 mg@kg-1@d-1,持续8周,并在MI后第2周心肌内分别注射培养基(3组)或诱导分化后的MSC(4组).MI后8周,结合心脏超声多普勒和血液动力学参数评价心功能.结果2、3两组间具有相似的心功能改善,即左室射血分数(LVEF)增加,左室舒张末期压(LVEDP)降低;2组左室前壁和间隔收缩速度增大,而3组无明显增加;4组与2组及3组相比,心功能改善更明显,表现在LVEF的增加更显著.结论单用诱导分化的MSC移植与单用ACEI治疗对兔MI后心功能的改善程度相似;而两者合用具有协同作用,能进一步改善兔MI后的心功能.

  17. Development of Bioartificial Myocardium Using Stem Cells and Nanobiotechnology Templates

    Juan Carlos Chachques


    Cell-based regenerative therapy is undergoing experimental and clinical trials in cardiology, in order to limit the consequences of decreased contractile function and compliance of damaged ventricles following myocardial infarction. Over 1000 patients have been treated worldwide with cell-based procedures for myocardial regeneration. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit adverse postischemic remodelling, and improve diastolic function. The deve...

  18. Strategies for recruitment of stem cells to treat myocardial infarction.

    Shafiq, Muhammad; Lee, Sang-Hoon; Jung, Youngmee; Kim, Soo Hyun


    Heart failure is one of the most prominent causes of morbidity and mortality worldwide. According to the World Health Organization, coronary artery disease and myocardial infarction (MI) are responsible for 29% of deaths worldwide. MI results in obstruction of the blood supply to the heart and scar formation, and causes substantial death of cardiomyocytes in the infarct zone followed by an inflammatory response. Current treatment methodologies of MI and heart failure include organ transplantation, coronary artery bypass grafting, ventricular remodeling, cardiomyoplasty, and cellular therapy. Each of these methodologies has associated risks and benefits. Cellular cardiomyoplasty is a viable option to decrease the fibrosis of infarct scars, adverse post-ischemic remodeling, and improve heart function. However, the low rate of cell survival, shortage of cell sources and donors, tumorigenesis, and ethical issues hamper full exploitation of cell therapy for MI treatment. Consequently, the mobilization and recruitment of endogenous stem/progenitor cells from bone marrow, peripheral circulation, and cardiac tissues has immense potential through harnessing the host's own reparative capacities that result from interplay among cytokines, chemokines, and adhesion molecules. Therapeutic treatments to enhance the mobilization and homing of stem cells are under development. In this review, we present state-of-the-art approaches that are being pursued for stem cell mobilization and recruitment to regenerate infarcted myocardium. Potential therapeutic interventions and delivery strategies are discussed in detail. PMID:25594408

  19. In vitro cardiomyogenic potential of human umbilical vein-derived mesenchymal stem cells

    Cardiomyocyte loss in the ischemically injured human heart often leads to irreversible defects in cardiac function. Recently, cellular cardiomyoplasty with mesenchymal stem cells, which are multipotent cells with the ability to differentiate into specialized cells under appropriate stimuli, has emerged as a new approach for repairing damaged myocardium. In the present study, the potential of human umbilical cord-derived mesenchymal stem cells to differentiate into cells with characteristics of cardiomyocyte was investigated. Mesenchymal stem cells were isolated from endothelial/subendothelial layers of the human umbilical cords using a method similar to that of human umbilical vein endothelial cell isolation. Isolated cells were characterized by transdifferentiation ability to adipocytes and osteoblasts, and also with flow cytometry analysis. After treatment with 5-azacytidine, the human umbilical cord-derived mesenchymal stem cells were morphologically transformed into cardiomyocyte-like cells and expressed cardiac differentiation markers. During the differentiation, cells were monitored by a phase contrast microscope and their morphological changes were demonstrated. Immunostaining of the differentiated cells for sarcomeric myosin (MF20), desmin, cardiac troponin I, and sarcomeric α-actinin was positive. RT-PCR analysis showed that these differentiated cells express cardiac-specific genes. Transmission electron microscopy revealed a cardiomyocyte-like ultrastructure and typical sarcomers. These observations confirm that human umbilical cord-derived mesenchymal stem cells can be chemically transformed into cardiomyocytes and can be considered as a source of cells for cellular cardiomyoplasty

  20. Transplantation of 5-azacytidine treated cardiac fibroblasts improves cardiac function of infarct hearts in rats

    TANG Cheng-chun; MA Gan-shan; CHEN Ji-yuan


    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 μmol/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 β-myosin heavy chain (β-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 β-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

  1. Justification for antioxidant preconditioning (or how to protect insulin-mediated actions under oxidative stress)

    A Orzechowski


    Insulin resistance is characterized by impaired glucose utilization in the peripheral tissues, accelerated muscle protein degradation, impaired antioxidant defences and extensive cell death. Apparently, both insulin and IGF-1 at physiological concentrations support cell survival by phosphatidylinositol 3 kinase-dependent and independent mechanisms. Postprandial hyperglycemia and hyperinsulinemia are found in insulin resistance, which accompanies the so-called noninsulin dependent diabetes mellitus (diabetes type 2). Evidence also indicates that increased susceptibility of muscle cells and cardiomycoytes to oxidative stress is among the harmful complications of insulin resistance and diabetes. Limited knowledge showing benefits of preconditioning with antioxidants (vitamin C, E, -lipoic acid, -acetylcysteine) in order to protect insulin action under oxidative stress prompted the author to discuss the theoretical background to this approach. It should be stressed that antioxidant preconditioning is relevant to prevention of both diabetes- and insulin resistance-associated side-effects such as low viability and cell deletion. Furthermore, antioxidant conditioning promises to provide higher efficacy for clinical applications in myoblast transfer therapy and cardiomyoplasty.

  2. Development of Bioartificial Myocardium Using Stem Cells and Nanobiotechnology Templates

    Juan Carlos Chachques


    Full Text Available Cell-based regenerative therapy is undergoing experimental and clinical trials in cardiology, in order to limit the consequences of decreased contractile function and compliance of damaged ventricles following myocardial infarction. Over 1000 patients have been treated worldwide with cell-based procedures for myocardial regeneration. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit adverse postischemic remodelling, and improve diastolic function. The development of a bioartificial myocardium is a new challenge; in this approach, tissue-engineered procedures are associated with cell therapy. Organ decellularization for bioscaffolds fabrication is a new investigated concept. Nanomaterials are emerging as the main candidates to ensure the achievement of a proper instructive cellular niche with good drug release/administration properties. Investigating the electrophysiological properties of bioartificial myocardium is the challenging objective of future research, associating a multielectrode network to provide electrical stimulation could improve the coupling of grafted cells and scaffolds with host cardiomyocytes. In summary, until now stem cell transplantation has not achieved clear hemodynamic benefits for myocardial diseases. Supported by relevant scientific background, the development of myocardial tissue engineering may constitute a new avenue and hope for the treatment of myocardial diseases.

  3. Surgery of congestive heart failure - the role of computed tomography in the pre- and postsurgical diagnostic evaluation; Chirurgie der Herzinsuffizienz - Stellenwert der Computertomographie in der prae- und postoperativen Diagnostik

    Lembcke, A.; Kivelitz, D.E.; Rogalla, P.; Dewey, M.; Klessen, C.; Hamm, B.; Enzweiler, C.N.H. [Inst. fuer Radiologie, Charite - Universitaetsmedizin Berlin, Charite Campus Mitte, Berlin (Germany); Dohmen, P.M.; Konertz, W.F. [Klinik fuer Kardiovaskulaere Chirurgie, Charite - Universitaetsmedizin Berlin, Charite Campus Mitte, Berlin (Germany); Wiese, T.H. [Inst. fuer Radiologie, Augusta-Kranken-Anstalt, Bochum (Germany)


    The treatment of advanced, drug resistant congestive heart failure gains in importance in the field of cardiac surgery. Cardiac imaging for preoperative assessment and follow-up focuses on the determination of ventricular volumes and function as well as on the detection of postoperative complications. Computed tomography (CT) is highly accurate irrespective of the individual patient's anatomic situation, has a low examiner dependence and short examination time, does not require an arterial vascular access and can be performed in patients with metal implants. CT is the modality of choice in the follow-up of heart transplants to detect extracardiac and cardiac complications including coronary calcifications as an early sign of transplant vasculopathy. In addition, CT visualizes the elements of mechanical assist devices and can identify their possible local cardiac and mediastinal complications CT can detect fibrolipomatous involution of the mobilized muscle flap in dynamic cardiomyoplasty and can depict fibrous reactions along the epicardial mesh implant in passive cardiac containment. Further indications include assessment of typical local postoperative complications, such as intrathoracic infection and mediastinal bleeding, intracardiac thrombus formation or pericardial effusion. CT is routinely used for evaluating bypass patency but is limited in assessing associated valve defects since it does not visualize flow. (orig.)

  4. Mesenchymal Stem Cells for Cardiac Regeneration: Translation to Bedside Reality

    Mohammad T. Elnakish


    Full Text Available Cardiovascular disease (CVD is the leading cause of death worldwide. According to the World Health Organization (WHO, an estimate of 17.3 million people died from CVDs in 2008 and by 2030, the number of deaths is estimated to reach almost 23.6 million. Despite the development of a variety of treatment options, heart failure management has failed to inhibit myocardial scar formation and replace the lost cardiomyocyte mass with new functional contractile cells. This shortage is complicated by the limited ability of the heart for self-regeneration. Accordingly, novel management approaches have been introduced into the field of cardiovascular research, leading to the evolution of gene- and cell-based therapies. Stem cell-based therapy (aka, cardiomyoplasty is a rapidly growing alternative for regenerating the damaged myocardium and attenuating ischemic heart disease. However, the optimal cell type to achieve this goal has not been established yet, even after a decade of cardiovascular stem cell research. Mesenchymal stem cells (MSCs in particular have been extensively investigated as a potential therapeutic approach for cardiac regeneration, due to their distinctive characteristics. In this paper, we focus on the therapeutic applications of MSCs and their transition from the experimental benchside to the clinical bedside.

  5. In Vitro Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Cardiomyocyte-like Cells

    Reihaneh Motamedi


    Full Text Available Objective: Human mesenchymal stem cells (MSCs have been recognized as potentialcandidates for cell therapy. In the present study, the ability of human bone marrow mesenchymalstem cells (hBMSCs to differentiate into cells with characteristics of cardiomyocytesin vitro was investigated.Materials and Methods: hBMSCs cultured in enriched medium were treated with oxytocinand 5-azacytidin. The differentiation of hBMSCs into cells that expressed cardiacspecificgenes such as α3-actinin, alpha - myosin heavy chain (α-MHC, beta - myosinheavy chain (β-MHC, myosin light chain isoform 2a (MLC2a, myosin light chain isoform2v (MLC2v, artial natriuretic factor (ANF, GATA4 and oxytocin receptor (OTR was investigatedby reverse transcription-polymerase chain reaction (RT-PCR. Protein expressionsof β-actinin and troponin I-C in the cells were analyzed through immunofluorescencestaining.Results: MSCs are spindle-shaped with irregular processes. Cells treated with oxytocinand 5-azacytidin connected with adjoining cells to form myotube-like structures. Expressionsof a number of cardiac-specific genes were detected by RT-PCR. Immunofluorescencestaining analysis showed that the differentiated cells stained positively for β-actininand troponin I-C protein.Conclusion: These results indicate that adult hBMSCs can differentiate into cardiomyocytesin vitro by treatment with oxytocin and 5-azacytidin, and can be considered as asource of cells for cellular cardiomyoplasty.

  6. Maintenance of HL-1 cardiomyocyte functional activity in PEGylated fibrin gels.

    Geuss, Laura R; Allen, Alicia C B; Ramamoorthy, Divya; Suggs, Laura J


    Successful cellular cardiomyoplasty is dependent on biocompatible materials that can retain the cells in the myocardium in order to promote host tissue repair following myocardial infarction. A variety of methods have been explored for incorporating a cell-seeded matrix into the heart, the most popular options being direct application of an injectable system or surgical implantation of a patch. Fibrin-based gels are suitable for either of these approaches, as they are biocompatible and have mechanical properties that can be tailored by adjusting the initial fibrinogen concentration. We have previously demonstrated that conjugating amine-reactive homo-bifunctional polyethylene glycol (PEG) to the fibrinogen prior to crosslinking with thrombin can increase stability both in vivo and in vitro. Similarly, when mesenchymal stem cells are combined with PEGylated fibrin and injected into the myocardium, cell retention can be significantly increased and scar tissue reduced following myocardial infarction. We hypothesized that this gel system could similarly promote cardiomyocyte viability and function in vitro, and that optimizing the mechanical properties of the hydrogel would enhance contractility. In this study, we cultured HL-1 cardiomyocytes either on top of plated PEGylated fibrin (2D) or embedded in 3D gels and evaluated cardiomyocyte function by assessing the expression of cardiomyocyte specific markers, sarcomeric α-actin, and connexin 43, as well as contractile activity. We observed that the culture method can drastically affect the functional phenotype of HL-1 cardiomyocytes, and we present data suggesting the potential use of PEGylated fibrin gel layers to prepare a sheet-like construct for myocardial regeneration. PMID:25657056

  7. Aptamer-based isolation and subsequent imaging of mesenchymal stem cells in ischemic myocard by magnetic resonance imaging

    Schaefer, R.; Hermanutz-Klein, U.; Northoff, H. [Universitaetsklinikum Tuebingen (Germany). Inst. fuer Klinische und Experimentelle Transfusionsmedizin; Wiskirchen, J.; Kehlbach, R.; Pintaske, J. [Universitaetsklinikum Tuebingen (Germany). Abt. fuer Radiologische Diagnostik; Guo, K.; Neumann, B.; Voth, V.; Walker, T.; Scheule, A.M.; Greiner, T.O.; Ziemer, G.; Wendel, H.P. [Universitaetsklinikum Tuebingen (Germany). Abt. fuer Thorax-, Herz- und Gefaesschirurgie; Claussen, C.D. [Universitaetsklinikum Tuebingen (Germany). Radiologische Universitaetsklinik


    Purpose: Mesenchymal stem cells (MSC) seem to be a promising cell source for cellular cardiomyoplasty. We recently developed a new aptamer-based specific selection of MSC to provide ''ready to transplant'' cells directly after isolation. We evaluated MRI tracking of newly isolated and freshly transplanted MSC in the heart using one short ex vivo selection step combining specific aptamer-based isolation and labeling of the cells. Materials and Methods: Bone marrow (BM) was collected from healthy pigs. The animals were euthanized and the heart was placed in a perfusion model. During cold ischemia, immunomagnetic isolation of MSC from the BM by MSC-specific aptamers labeled with Dynabeads {sup registered} was performed within 2 h. For histological identification the cells were additionally stained with PKH26. Approx. 3 x 10{sup 6} of the freshly aptamer-isolated cells were injected into the ramus interventricularis anterior (RIVA) and 5 x 10{sup 5} cells were injected directly into myocardial tissue after damaging the respective area by freezing (cryo-scar). 3 x 10{sup 6} of the aptamer-isolated cells were kept for further characterization (FACS and differentiation assays). 20 h after cell transplantation, MRI of the heart using a clinical 3.0 Tesla whole body scanner (Magnetom Trio, Siemens, Germany) was performed followed by histological examinations. Results: The average yield of sorted cells from 120 ml BM was 7 x 10{sup 6} cells. The cells were cultured and showed MSC-like properties. MRI showed reproducible artifacts within the RIVA-perfusion area and the cryo-scar with surprisingly excellent quality. The histological examination of the biopsies showed PKH26-positive cells within the areas which were positive in the MRI in contrast to the control biopsies. Conclusion: Immunomagnetic separation of MSC by specific aptamers linked to magnetic particles is feasible, effective and combines a specific separation and labeling technique to a &apos

  8. Ventriculectomia parcial: um novo conceito no tratamento cirúrgico de cardiopatias em fase final Partial ventriculectomy: a new concept for surgical treatment of end stage cardiopathies

    Randas J. V Batista


    Full Text Available A melhora clínica da função cardíaca pós aneurismectomia de ventrículo esquerdo e/ou cardiomioplastia com o músculo grande dorsal parece ser, ao menos parcialmente, devida ao remodelamento do ventrículo esquerdo. Através de pesquisa em nosso laboratório experimental com carneiros, demonstramos que o aumento do diâmetro do ventrículo é mais importante que a perda de massa muscular para a deterioração da função ventricular. Sabendo-se que em miocardiopatia dilatada não ocorre aumento de massa muscular, reduzimos o diâmetro do ventrículo para o normal, em uma série consecutiva de pacientes com esta lesão. No período de 1984 a 1995, foram operados com esta nova técnica, denominada, então, "Ventriculectomia Parcial", 103 pacientes portadores de miocardiopatias complexas e insuficiência cardíaca congestiva (NYHA IV. A operação é baseada na lei de Laplace (T=P.11.D e consistiu na remoção de uma fatia de músculo da parede lateral do ventrículo esquerdo, iniciando-se na ponta deste, estendendo-se entre os músculos papilares e terminando próximo ao anel mitral. A cirurgia é realizada sob circulação extracorpórea normotérmica e não se utiliza cardioplegia. "Todos os pacientes foram avaliados pré-operatoriamente com ecodopplercardiografia e ventriculografia digital, os quais revelaram fração de ejeção The clinical improvement of cardiac function post left ventricular aneurysmectomy and/or cardiomyoplasty with the latissimus dorsi muscle seems to be due to the remodeling of the left ventricle. We did some experiments with sheep in our laboratory and we concluded that the increment of ventricular diameter is more deleterious than loss of muscle mass to the ventricular function. Since there is no increment in muscle mass to the dilated hearts, we reduced their diameter to accomplish a better ventricular function in a series of very sick patients with dilated hearts. From 1984 to 1995, 103 patients with complex