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Introduction. Heart failure as a result of ischemic myocardial remodeling is one of the most severe diseases with poor prognosis. Drug therapy alone with surgical or percutaneous revascularization of damaged myocardium often fails to achieve optimum effect in the treatment of the mentioned syndrome. Cell cardiomyoplasty using autologous bone marrow derived mesenchymal stem cells (BM-MSCs) has already proved to be promising alternative to both these treatment methods, as it’s aimed directly at restoration of normally functioning myocard. The aim. To study the effects of different techniques of cardiomyoplasty with BM-MSCs on morphometrical and functional indices of post-infarctional left ventricular remodeling in experiment. Materials and methods. An experimental model of myocardial infarction in laboratory rats was used for the research. The survived animals were equally divided into 5 groups; the animals of 3 groups underwent BM-MSC transplantation. A certain technique of cardiomyoplasty was used in each of the 3 groups: direct injection into necrotic myocardium, intravenous injection and injection inside left ventricular cavity (which imitates intracoronalintroduction). Other 2 groups were comparison groups where the animals did not achieve BM-MSCs after infarction. There was also control group with intact animals with normal values of all the studied indices. The following invasive and noninvasive measurements of functional heart indices have been done in all research groups: left ventricular weight and its relation to body weight, end-systolic and end-diastolic left ventricular internal dimensions, fractional shortening, ejection fraction, stroke volume, heart rate, systemic arterial pressure and left ventricular inner pressure, both systolic and diastolic. The follow-up period was 1 and 3 months after the experiment. Finally, all animals were euthanized and autopsied, and the results of macroscopic examination of their hearts have been matched with aforecited functional indices in each group. Results and discussion. The analysis of all measured parameters and their comparison between groups have revealed that BM-MSC transplantation (irrespective of technique) conduces to reliably significant retention of functioning myocardium volume, reliably significant improvement of contractility parameters, particularly, reduced end-systolic and end-diastolic internal dimensions, increased ejection fraction, fractional shortening and stroke volume; it also contributes to maximal inalterability of such hemodynamic parameters as heart rate, systemic arterial pressure, left ventricular inner pressure. In addition, in all 3 groups of cell therapy the indices of contractility and pump function of the left ventricle were very close to normal rates. But the optimal results have been obtained in the group of direct intramyocardial injections. Conclusion. Cell cardiomyoplasty with BM-MSCs tends to prevent ischemic myocardial remodeling and, as a result, to improve myocardial contractility and neutralize manifestations of severe heart failure in short-term follow-up of 1 and 3 months.

An inspiring scientific cooperation has come to an end, when Gerta Vrbová, an internationally renowned researcher in the field of neuromuscular interactions, passed away on October 2, 2020. Comparative EMG studies had led Gerta to suggest that different contractile properties of fast- and slow-twitch muscle fibers relate to specific firing patterns of their motoneurones. In support of her hypothesis, long term stimulation of fast-twitch muscles with a stimulus pattern resembling that of slow motoneurones, were shown to induce a pronounced fast-to-slow shift in contractile properties. In our cooperation which started in 1970, and also in cooperation with others, Gerta's experiment proved to be an ideal model for the study of neurally controlled changes in phenotype characteristics at various levels of molecular and cellular organization, their time courses and ranges. It has become most important in basic research on the adaptive potential or plasticity of muscle.

This article reviews the concept and extensive experimentation done over two decades ago to convert and apply skeletal muscle for cardiac assistance—so called “cardiomyoplasty”. Skeletal muscle was either wrapped around a failing heart or fashioned into accessory cardiac pumping chambers. Although the era of cardiomyoplasty came to an end when the cardiac wraps were found ineffective, the concept of independent accessory skeletal muscle ventricles may be worth another look.

Heart failure is a heterogeneous clinical syndrome that develops after an "index event" which damages cardiac tissue with loss of cardimyocytes and/or alteration of myocardial ability to generate an efficient ventricular contraction. The initial injury can appear suddenly as in the acute coronary syndrome or gradually as happens in chronic coronary arteries disease, and primary or secondary cardiomyopathies. Regardless of the etiologic factor, a series of hemodynamic alterations and neurohormonal responses with complex molecular changes is produced, leading to progression of ventricular dysfunction and to greater loss of contractile cells due to necrosis or apoptosis. Therapeutic strategies developed so far to interrupt this vicious circle of myocardial dysfunction and ventricular remodeling, do change the conditions of myocardial work, improving the situation of patients and their survival probability. However, this therapeutic approach does not produce myocardial regeneration, and consequently, the disease may progress to terminal heart failure and death. Experimental and clinical studies have revealed that implantation of bone marrow stem cells may produce angiogenesis and improve cardiac function in patients with acute or chronic ischaemic heart disease. It has been found that this therapy produces significant improvement of several parameters such as: symptoms, exercise capacity, functional state, size of the myocardial perfusion defect and ejection fraction; besides, there is a decrease in the end-systolic left ventricle volume. The procedure is not associated with complications. In conclusion, bone marrow stem cells transplantation is an effective and safe form of therapy to promote neovascularization and improve myocardial perfusion and contractility in patients with acute or chronic ischaemic heart disease who are not appropriate candidates for standard revascularization therapies. La falla cardíaca es un síndrome clínico heterogéneo que se desarrolla después de un "evento índice", el cual produce daño del tejido muscular cardíaco por la pérdida de cardiomiocitos o por la alteración de la capacidad del miocardio para generar una fuerza eficiente para la contracción ventricular. La noxa inicial puede ser de aparición súbita como en el síndrome coronario agudo o insidiosa y gradual como en la enfermedad coronaria crónica y las cardiomiopatías primarias y secundarias. Independiente del factor que genere el síndrome, se produce una serie de respuestas hemodinámicas y neurohormonales con cambios moleculares complejos, que conducen a la progresión de la disfunción ventricular y a mayor pérdida de células contráctiles funcionantes por necrosis o por apoptosis. Las estrategias terapéuticas desarrolladas para interrumpir este círculo vicioso de disfunción miocárdica y remodelación ventricular, cambian las condiciones en que se produce el trabajo miocárdico, con la consecuente mejoría de la enfermedad y de la tasa de supervivencia. Sin embargo, este enfoque terapéutico, conocido como la "aproximación Jurásica", no logra recuperar el tejido lesionado durante el proceso, lo que permite la progresión de la enfermedad hasta llegar a la falla cardíaca terminal y la muerte. Estudios experimentales y clínicos han demostrado que la implantación de células progenitoras derivadas de la médula ósea producen angiogénesis y recuperación de la función cardíaca en pacientes con cardiopatía isquémica aguda y crónica. Con esta terapia se ha demostrado mejoría significativa de la sintomatología, de la capacidad funcional, del estado funcional, del tamaño del defecto de perfusión miocárdica medido por pruebas de medicina nuclear y de la fracción de eyección al igual que disminución del volumen sistólico final del ventrículo izquierdo, sin complicaciones relacionadas con el procedimiento. En conclusión, el trasplante de células progenitoras derivadas de la médula ósea es una terapia efectiva y segura para promover la neovascularización y mejorar la contractilidad y la perfusión miocárdicas en los pacientes con cardiopatía isquémica aguda o crónica, que sean pobres candidatos para la cirugía.

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 média do VE foi de 19,37±3,48%. A mortalidade hospitalar foi de 2,2% e 39 pacientes, que completaram o período de condicionamento, tiveram seguimento médio de 46±26 meses. Vinte e oito pacientes foram mantidos predominantemente sob estimulação em modo 1:1 e 11 pacientes foram mantidos predominantemente sob estimulação em modo 1:2. RESULTADOS: A sobrevivência foi de 9% em nove anos. As causas de óbito foram progressão da insuficiência cardíaca e morte súbita. A classe funcional, o índice de resistência vascular pulmonar e o modo de estimulação foram identificados como fatores independentes de prognóstico. A manutenção da melhora da fração de ejeção do VE em relação ao pré-operatório foi mais consistente ao longo do período estudado, quando o enxerto muscular foi estimulado em modo 1:2. CONCLUSÃO: Os resultados tardios da cardiomioplastia dinâmica são limitados pela alta incidência de morte súbita e de óbitos decorrentes da progressão da doença de base. A sobrevivência é influenciada pela condição clínica pré-operatória e pelo modo de estimulação do enxerto. O desempenho do enxerto muscular é mais satisfatório a longo prazo quando submetido à estimulação modo 1:2.

OBJECTIVE: To study the effect of propafenone on the contractile function of latissimus dorsi muscle isolated from rats in an organ chamber. METHODS: We studied 20 latissimus dorsi muscles of Wistar rats and divided them into 2 groups: group I (n=10), or control group - we studied the feasibility of muscle contractility; group II (n=10), in which the contralateral muscles were grouped - we analyzed the effect of propafenone on muscle contractility. After building a muscle ring, 8 periods of sequential 2-minute baths were performed, with intervals of preprogrammed electrical stimulation using a pacemaker of 50 stimuli/min. In group II, propafenone, at the concentration of 9.8 µg/mL, was added to the bath in period 2 and withdrawn in period 4. RESULTS: In group I, no significant depression in muscle contraction occurred up to period 5 (p>0.05). In group II, a significant depression occurred in all periods, except between the last 2 periods (p0.05). CONCLUSION: Propafenone had a depressing effect on the contractile function of latissimus dorsi muscle isolated from rats and studied in an organ chamber.

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 in 34 patients with idiopathic dilated cardiomyopathy submitted to this procedure from May 1988 to September 1994. Twenty seven patients were in New York Heart Association functional class III and 7 were in class IV before the operation, despite the use of maximal medical therapy. Hospital mortality was 2.9% and 1 patient presenting heart failure progression was submitted to urgent heart transplantation 42 days after cardiomyoplasty. The other patients were followed-up from 2 to 73 months (mean, 27.4 months). At 6 months of follow-up, 12 patients were in functional class 1,15 patients in class II and 3 patients in class III (p=0.001, in relation to preoperative data). Similar findings were observed from one to four years of follow-up. On the other hand, 14 patients died up to 5 years after the operation and the survival rates were 84.7% at 1 year, 67.7% at 2 years and 39.9% at 5 years of follow-up. The cause of death was progression of heart failure in 9 patients and 5 patients died suddenly. By stepwise Cox regression method, patients operated in functional class IV had relative risk of death 5.5 times higher than class III patients (p=0.006), whose survival rate was 52.7% at 5 years of followup. Regarding cardiomyoplasty influence on ventricular function, radioisotopic left ventricular (LV) ejection fraction improved from 19.8 + 3.1% to 23.6 + 6.2%, at 6 months of follow-up. Doppler-echocardiography documented similar changes in LV wall shortening. Also, right heart catheterization showed significant increases in mean arterial pressure, stroke index and LV stroke work index, which were associated with the decrease of mean pulmonary wedge pressure. On the other hand, it was not found any significant postoperative change in ventricular arrhythmia and atrial fibrillation incidence. At the late postoperative period, the hemodynamic improvement was maintained up to 5 years of follow-up, while LV ejection fraction and wall shortening tended to decrease after the second postoperative year returned to the preoperative levels. Finally, 3 of the 5 patients who completed 5 years of follow-up died due to heart failure progression and other died suddenly up to 73 months after the operation. Furthermore, histological examinations showed important fat tissue infiltration in the skeletal muscle flap of 9 patients submitted to necropsy studies from 20 to 73 months of follow-up. These histological changes were more severe in patients with longer follow-up. In conclusion, dynamic cardiomyoplasty improves congestive heart failure and LV function in patients with idiopathic dilated cardiomyopathy. However, long-term survival after this procedure is limited in patients operated upon in functional class IV. Furthermore, the cardiomyoplasty benefits on left ventricular function appear to be limited to a midterm period and this fact may be associated with late muscle flap degeneration.

Na cardiomioplastia, a contração do músculo esquelético, submetido à estimulação elétrica sobre a parede ventricular dilatada, aumenta a função ventricular, que é dependente das condições prévias do coração e da doença de base. Um dos problemas principais que interfere no sucesso da substituição do músculo cardíaco é a estimulação sincrónica do miocárdio e o músculo esquelético. A estimulação desse músculo a longo prazo tem sido possível graças a eletrodos especiais associados à estimulação progressiva seqüencial, adaptando-o à função cardíaca, através da transformação gradual de fibras glicolíticas expostas à fadiga em oxidativas lentas altamente resistentes. O gerador de pulsos "Myos" (Biotronik) tem sido utilizado em nosso Serviço para estimulação elétrica do músculo grande dorsal em sincronização com o miocárdio. Esse tipo de cardiomioestimulador com circuito eletrônico e bateria de lítio armazena um programa de estimulação responsável por diferentes modos operacionais, adaptados por um programa de computação. Para a programação do cardiomioestimulador, o momento da sincronização do trem de pulso com a abertura da valva aórtica é de extrema importância. O modo M de alta velocidade é utilizado para avaliar este sincronismo. A avaliação clínica da cardiomioplastia tem como base os resultados obtidos de 32 pacientes, com idade de 22 a 72 anos (média = 46,2 anos). A maioria (72%) dos pacientes apresentou miocardiopatia dilatada por causa indeterminada, 24% de origem chagásica, 3% virótica e 3% por periparto. Os índices de mortalidade hospitalar e tardia foram ambos de 12,5% e de 3,1%, respectivamente, excluindo-se os chagásicos. A sobrevida atuarial foi de 81,3+-0,22% após 6 anos e de 94.4+-0,1 % após 5 anos, retirando-se os chagásicos. Os índices médios de diâmetros sistólico (55,1 mm), diastólico (70,7 mm), encurtamento segmentar (22,8%) e fração de ejeção (51,0%), 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 diameters (55,1 mm), diastolic (70,7 mm), segmental shortening (22.8%) and ejection fraction (51.0%), related to an average follow-up of 14.2 months, reflect that the cardiomyoplasty can be effective to assist the left ventricle. Choosing the right patient seems to be key to the goog operative result in short and long terms.

A cardiomioplastia melhora a função ventricular esquerda e a sobrevida de pacientes portadores de cardiomiopatias severas. O objetivo deste estudo é identificar os fatores que influenciaram os resultados da cardiomioplastia em 22 pacientes operados entre maio de 1988 e dezembro de 1991. Todos os pacientes estavam em classe funcional III ou IV, apesar do uso de terapêutica clínica otimizada. Dezoito pacientes tinham diagnóstico de cardiomiopatia idiopática, a cardiomiopatia era chagásica em 2 e isquémica em 2. Não houve óbitos no período pós-operatório imediato e os pacientes foram seguidos por um período médio de 20,5 meses. Nove pacientes faleceram tardiamente e a sobrevida atuarial foi 76,1 % no primeiro ano e 63,8% no segundo ano de seguimento. Seis pacientes estão, atualmente, em classe funcional I, e 7 em classe II. A mortalidade e a manutenção dos sintomas, no primeiro ano pós cardiomioplastia, foi relacionada a ocorrência de tromboembolismo pulmonar e a progressão da insuficiência cardíaca em pacientes com alterações isquémicas do enxerto muscular, no pós-operatório imediato (pico de liberação plasmática da creatinoquinase > 1500 U.I.) (p=0,03). Paralelamente, aelevaçáo da fração de ejeção do ventrículo esquerdo, documentada aos seis meses de seguimento, foi mais importante em pacientes que apresentaram valores menores de liberação da creatinoquinase após a operação (p=0,02). Já o tamanho da cavidade ventricular esquerda pareceu influenciar a variação da fração de ejeção apenas quando foram retirados da análise os pacientes com comprometimento importante do enxerto muscular (p=0,06). Apesar de não ter havido influência da classe funcional pré-operatória sobre esse parâmetro e sobre a evolução clínica, no primeiro ano de seguimento, os pacientes operados em classe funcional IV apresentaram uma sobrevida, no segundo ano de pós-operatório, significativamente inferior à dos pacientes operados em classe III (33,3% versus 78,1%, p=0,04). Em conclusão, a melhora da função ventricular esquerda e a melhor evolução clínica após a cardiomioplastia podem ser limitadas pela ocorrência de lesão isquémica do enxerto muscular. A condição clínica pré-operatória, bem como o grau de dilatação das câmaras ventriculares, são, também, fatores importantes para o sucesso deste procedimento no tratamento das cardiomiopatias.Dynamic cardiomyoplasty improves left ventricular function and survival of patients with severe cardiomyopathies. The purpose of this study was to investigate the factors influencing cardiomyoplasty results in 22 patients operated upon at the Heart Institute. All patients were in New York Heart Association class III or IV, despite the use of maximal medical therapy. Eighteen patients had idiopathic dilated cardiomyopathy, in two patients the cardiomyopathy was due to Chagas' disease and in two due to ischemic ethiology. There were no operative death and patients were followed up for a mean of 20.5 months. Nine patients died at late follow-up period, and actuarial survival rates were 76.1% at 1 year and 63.8% at 2 years of follow-up. Six patients are presently in functional class I and six in class II. The mortality and the absence of functional improvement at 1 year were associated to episodes of pulmonary thromboelbolysm and to heart failure progression in patients with severe muscle flap ischemic compromise at the immediate postoperative period (creatinokinase peak level > 14001. U.) (p=0.03). In addition, the improvement of left ventricular ejection fraction at 6 months of follow-up was more significant in patients who presented lower values of creatinokinase after the surgical procedure (p=0.02). Otherwise, the influence of left ventricular dimension on ejection fraction changes was documented only when patients with severe muscle flap compromise were withdrawn from the analysis (p=0.06). Despite the absence of functional class influence on 1 year results of cardiomyoplasty, patients operated upon in class IV presented a less significant survival than patients operated upon in class III at 2 years of follow-up (33.3% versus 78.1 %, p= 0.04). In conclusion, quality of life and left ventricular function improvement after cardiomyoplasty may be limited by muscle flap ischemic compromise. Patient's condition prior to surgery and the degree of left ventricular dilation may also influence cardiomyoplasty results in patients with severe cardiomyopathies.

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 < 0,01), sendo que esse parâmetro se alterou principalmente em pacientes com menor dilatação da câmara ventricular esquerda. A Doppler-ecocardiografia mostrou que o encurtamento segmentar do ventrículo esquerdo se elevou de 12 ± 3,1 para 17,8 ± 2,3% (p < 0,01), enquanto que o volume sistólico aumentou de 23,6 ± 5,2 para 32,3 ± 7,9 ml (p < 0,01). Elevações semelhantes do índice sistólico, associados à queda da pressão em território pulmonar, foram também observadas pelo cateterismo cardíaco. O estudo ergoespirométrico documentou o aumento do consumo máximo de oxigênio de 14,9 ± 3,9 para 18,2 ± 3,4 ml/kg/min (p < 0,05). Um ano e aos 18 meses após a operação, as alterações decorrentes da cardiomioplastia permaneceram essencialmente as mesmas. Em conclusão, a cardiomioplastia melhora a função ventricular esquerda, reverte o quadro congestivo e melhora a sobrevida de pacientes portadores de cardiomiopatia dilatada. Fatores como a existência de grande cardiomegalia podem, contudo, influenciar a evolução tardia dos pacientes submetidos a este procedimento.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 surviving patients in cardiomyoplasty group are in NYHA Class I and six in Class II. At 6 months of follow-up, radioisotopic left ventricular (LV) ejection fraction increased from 20.1 ± 3.8 to 26 ± 7.8% (p < 0.01). Doppler-echocardiography demonstrated that LV segmental wall shortening improved from 12 ± 3.1 to 17.8 ± 2.3% (p < 0.01), while LV stroke volume increased from 23.6 ± 5.2 to 32.3 ± 7.9 ml (p < 0.01). Similar increases in cardiac index, associated with decreases in pulmonary artery and wedge pressures, were also demonstrated by cardiac catheterization. Cardiopulmonary exercise test showed the improvement of maximal oxygen consumption from 14,9 ± 3.9 to 18.2 ± 3.4 ml/kg/min (p < 0.05). One year and 18 months after the cardiomyoplasty, these data remained essentially unchanged. In conclusion, dynamic cardiomyoplasty improves left ventricular function, reverses congestive heart failure and may improve survival of patiens with dilated cardiomyopathies. Factors as the existence of severe left ventricular dilation may, however, limited the late results of this procedure.

A utilização de enxertos musculares esqueléticos, estimulados síncronamente ao coração, para substituir ou envolver o miocárdio, tem sido apontada como uma nova alternativa no tratamento das cardiomiopatias terminais. No Instituto do Coração, 5 pacientes portadores de cardiomiopatia dilatada, com sintomas de insuficiência cardíaca congestiva, refratários à terapêutica medicamentosa, foram submetidos a cardiomioplastia, no período de maio a dezembro de 1988. Em 1 dos casos, a etiologia era chagásica e, nos demais, idiopática. A operação constou do envolvimento dos ventrículos direito e esquerdo pelo músculo grande dorsal esquerdo e do implante do sistema de estimulação muscular. Não houve óbitos, no período pós-operatório imediato e, em 1 dos casos, ocorreu perda da resposta contrátil do enxerto muscular, tendo o paciente falecido por insuficiência miocárdica, 2 meses após a operação. Os outros 4 pacientes foram seguidos por 4 a 9 meses, sendo constatada melhora do quadro clínico e do desempenho físico, associada a menor necessidade de medicamentos, em relação ao pré-operatório. A angiografia radioisotópica demonstrou aumento da fração de ejeção do ventrículo esquerdo, com estimulação do grande dorsal em 43 ± 3% e a avaliação hemodinâmica documentou elevação do trabalho sistólico daquela câmara, associada à queda da pressão capilar pulmonar, após a cardiomioplastia. Por outro lado, foi tam jém observada diminuição da capacidade vital em 15 ± 4%, não sendo identificada, contudo, qualquer limitação clínica decorrente desse fato. Em conclusão, a cardiomioplastia pode aumentar a contrátil idade das câmaras ventriculares em pacientes com cardiomiopatia dilatada, facilitando o controle do quadro congestivo. Este estudo sugere, ainda, que essa técnica pode ser realizada com baixa mortalidade imediata e que a morbidade do procedimento parece estar restrita à possibilidade de perda do enxerto e às alterações da função pulmonar decorrentes da presença do grande dorsal no interior do tórax.Cardiomyoplasty is a new approach to the treatment of cardiac insufficiency and its objetive is a control of congestive failure state by the increase of ventricular pumping performance due to improved contractility of the failing heart. At the Heart Institute, from May to December of 1988, latissimus dorsi cardiomyoplasty was performed in 5 patients with dilated cardiomyopathy. The patients were in NYHA. class III or IV despite maximal medical therapy. Etiology was idiopathic in four and due to Chagas' disease in one patient. The mean cardiothoracic ratio was 58 ± 2% and the resting left ventricular ejection fraction (Thecnetium) ranged from 19 to 29%. The operation was performed without extracorporeal circulation and the left latissimus dorsi muscle was wrapped around the right and left ventricles. There were no operative deaths. On the other hand, the loss of muscle flap contraction occurred in one patient due to latissimus dorsi ischemia and this patient died two months later in congestive heart failure. In follow-up ranging from 4 to 9 months, 4 patients that completed the muscle conditioning protocol were in NYHA class I or II with lesser amounts of drugs. Maximal oxygen consumption in treadmill test increased from 13.4 ± 0.8 to 20.6 ± 2.3 ml/min/kg and resting ejection fraction from 23.7 ± 4.2 to 34 ± 7.3%. Hemodynamic evaluation showed that pulmonary wedge pressure decreased from 23.5 ± to 13.2 ± 5.4 mmHg and that stroke work index increased from 15.8 ± 4.2 to 26 ± 7.4 g.M/M². Finally, pulmonary functional test showed that vital capacity decreased 15 ± 4% and a reduction of left lung ventilation was observed after cardiomyoplasty. From these findings, we conclude that cardiomyoplasty may improve ventricular function in patients with dilated cardiomyopathy, leading to reversion of congestive failure. Surgical morbidity appears to be restricted to muscle flap damage and pulmonary function changes due to muscle flap presence in the left hemithorax.

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 conditioned Latissimus Dorsi and the effectiveness of stimulated preconditioned skeletal muscle flaps wrapped around the heart to restore ventricular contractility in presence of myocardial dysfunction. Thirteen adult mongrel dogs were studied after burst stimulation of left Latissimus Dosi for six to eight weeks. In seven animals, conditioned muscles were compared with unconditioned contralateral controls by isometric force development. Normal and transformed muscles exhibited the same optimum pacing parameters (burst frequencies from 5o Hz up, train duration from 150 ms up). Conditioned muscles showed a smaller force (-27%) and a longer contraction time (+32%). Fatigue curves of unconditioned muscles under different duty cycles showed marked initial decrease and inversely proportional stable values of force after some minutes with equal final tension time indexes (18 ± 2 KgF. seg/min). Conditioned Latissimus Dorsi maintained stable force during prolonged stimulation under same conditions with a greater tension time index (68 ± 6 KgF. seg/min). The other six animals were submited to cardiomyoplasty; hemodynamic and echocardiographic evaluation were performed after induction of myocardial dysfunction by betablockers administration and volume loading. With synchronous pulse train stimulation increases of cardiac index by an average of 36 ± 4% (p

ABSTRACT Cardiovascular diseases are the major cause of death worldwide. The heart has limited capacity of regeneration, therefore, transplantation is the only solution in some cases despite presenting many disadvantages. Tissue engineering has been considered the ideal strategy for regenerative medicine in cardiology. It is an interdisciplinary field combining many techniques that aim to maintain, regenerate or replace a tissue or organ. The main approach of cardiac tissue engineering is to create cardiac grafts, either whole heart substitutes or tissues that can be efficiently implanted in the organism, regenerating the tissue and giving rise to a fully functional heart, without causing side effects, such as immunogenicity. In this review, we systematically present and compare the techniques that have drawn the most attention in this field and that generally have focused on four important issues: the scaffold material selection, the scaffold material production, cellular selection and in vitro cell culture. Many studies used several techniques that are herein presented, including biopolymers, decellularization and bioreactors, and made significant advances, either seeking a graft or an entire bioartificial heart. However, much work remains to better understand and improve existing techniques, to develop robust, efficient and efficacious methods.