Diagnostic methodology of cardiac dynamics based on the Zipf-Mandelbrot law: evaluation with 50 patients / Metodología diagnóstica de la dinámica cardiaca basada en ley de Zipf-Mandelbrot: evaluación con 50 pacientes

Abstract: Objective: Zipf-Mandelbrot law has been used to assess the complexity of cardiac systems. The objective of this work is to corroborate the clinical applicability of a diagnostic methodology developed from Zipf-Mandelbrot law, in the differentiation of normality and acute cardiac disease. Material and methods: there were taken 50 continuous electrocardiographic Holter monitoring records, 20 normal and 30 with acute alterations of the cardiac dynamics. The frequencies of occurrence of heart rates in ranges of 15 lat/min were organized hierarchically to demonstrate the hyperbolic behavior of dynamics and to apply the Zipf-Mandelbrot law. A linearization was performed and the statistical fractal dimension of each dynamic was obtained, giving rise to the mathematical diagnosis. Sensitivity, specificity and Kappa coefficient were calculated. Results: The values of the statistical fractal dimension of the acute cardiac dynamics were between 0.7123 and 0.9327, whereas for the normal dynamics were found between 0.4253 and 0.6698, evidencing quantitative differences between states of normality and disease. Sensitivity and specificity values of 100% were found and the kappa coefficient was 1. Conclusions: The clinical and diagnostic utility of the mathematical methodology based on Zipf-Mandelbrot law was verified, observing a decrease of dynamics complexity in cases of acute heart disease.(AU)

Resumen: Objetivo: La ley de Zipf-Mandelbrot ha sido utilizada con el fin de evaluar la complejidad de los sistemas cardiacos. El objetivo de este trabajo es corroborar la aplicabilidad clínica de una metodología diagnóstica desarrollada a partir de la ley de Zipf-Mandelbrot, en la diferenciación de normalidad y enfermedad cardiaca aguda. Material y métodos: Se tomaron 50 Holter cardiacos (monitoreo electrocardiográfico continuo ambulatorio), 20 normales y 30 con alteraciones agudas de la dinámica cardiaca. Se organizaron jerárquicamente las frecuencias de aparición de frecuencias cardiacas en rangos de a 15 lat/min, para evidenciar el comportamiento hiperbólico de las dinámicas y aplicar la ley de Zipf-Mandelbrot. Se realizó una linealización y se obtuvo la dimensión fractal estadística de cada dinámica, dando lugar al diagnóstico matemático. Fueron calculadas la sensibilidad, especificidad y el coeficiente Kappa. Resultados: Los valores de la dimensión fractal estadística de las dinámicas cardiacas agudas se encontraron entre 0.7123 y 0.9327, mientras que para las dinámicas normales se hallaron entre 0.4253 y 0.6698, evidenciando diferencias cuantitativas entre estados de normalidad y enfermedad. Se encontraron valores de sensibilidad y especificidad del 100% y el coeficiente kappa fue de 1. Conclusiones: Fue comprobada la utilidad clínica y diagnóstica de la metodología matemática basada en la ley de Zipf-Mandelbrot, observando un decremento de la complejidad de la dinámica en casos de enfermedad cardiaca aguda.(AU)

Surgical treatment with modified Morrow procedure in hypertrophic obstructive cardiomyopathy / 中华外科杂志

<p><b>OBJECTIVE</b>To summarize the experience of ventricular septal myectomy (modified Morrow procedure) in patients with hypertrophic obstructive cardiomyopathy (HOCM).</p><p><b>METHODS</b>From June 2003 to March 2011, 38 patients (26 male and 12 female) with HOCM underwent modified Morrow procedure. The mean age was 36.3 years (ranging from 18 to 64 years). The diagnosis was made by echocardiography and spiral CT. The mean systolic gradient between the left ventricle and the aorta from transthoracic echocardiography (TTE) was (89±31) mmHg (ranging from 50 to 184 mmHg, 1 mmHg=0.133 kPa) before operation. There was moderate or severe systolic anterior motion (SAM) in 38 cases and mitral regurgitation in 29 cases. Ventricular septal myectomy with modified Morrow procedure was performed in all 38 cases. TEE was used intraoperatively to evaluate the results of the surgical procedures. After 1 to 2 weeks of operation, TTE was performed to evaluate the effect of operation. All patients were followed up with TTE after operation.</p><p><b>RESULTS</b>All patients were discharged without complications. Intraoperative TEE showed that the mean systolic gradient between the left ventricle and the aorta was decreased from (95±36) mmHg before procedures to (14±11) mmHg after operation (t=13.265, P=0.000), and the thickness of ventricular septum was decreased from (28±8) mm to (12±3) mm (t=11.656, P=0.000). TTE showed that the mean systolic gradient between the left ventricle and the aorta was decreased from (89±31) mmHg preoperatively to (18±13) mmHg (t=12.729, P=0.000) in 1 to 2 weeks after operation. Mitral regurgitation and SAM were significantly improved or disappeared (t=7.930, t=5.213, both P=0.000). During the follow-up, all patients promptly became completely asymptomatic or complained of mild effort dyspnea only and syncope was abolished, and TTE showed that the pressure gradient was kept on the postoperative level or slightly decreased (P=0.494).</p><p><b>CONCLUSIONS</b>Ventricular septal myectomy with modified Morrow procedure is a mostly effective method for patients with HOCM. Good surgical exposure and the hypertrophied septum thoroughly excised are paramount for successful surgery.</p>

Cardiomioplastia e artefatos no eletrocardiograma / Cardiomyoplasty and artifacts in the electrocardiogram

Trata-se de uma paciente portadora de insuficiência cardíaca refratária ao tratamento convencional, na qual foi realizada cardiomioplastia do músculo torácico grande dorsal. O músculo era estimulado por marca-passo implantado e os estímulos marcavam no ECG aspectos de artefatos. O ECG se apresenta com os artefatos incidindo sobre o seguimento S-T a cada dois ciclos por segundo, com aspecto inusitado.

A female patient with refractory cardiac failure not respondng to conventional treatment underwent cardiomyoplasty using the latissimus dorsi muscle toimprove cardiac contractions. The muscle was stimuated by an implanted pacemaker with the stimuli presentingaspects of artifacts in the ECG, which registered artifacts in the S-T segment at two cycles per second, with an unsual appearance.

Asistencia y regeneración del miocardio combinando terapia celular e ingeniería de tejidos. Resultados del estudio clínico MAGNUM / Myocardial regeneration and asistance combined cardiac tissue engineering and stem cell therapy. Outcome of trial MAGNUM

Objetivos. El trasplante celular para la regeneración del miocardio está limitado por la escasa viabilidad del injerto y la baja retención celular. En la miocardiopatía isquémica la matriz extracelular está profundamente alterada, por consiguiente, sería importante asociar un procedimiento para regenerar las células miocárdicas y restaurar la función de la matriz extracelular. En este estudio clínico, fue evaluada la terapia celular intrainfarto asociada a una matriz de colágeno sembrada con células e implantada sobre ventrículos infartados.Métodos. En 15 pacientes (54,2±3,8 años de edad) que presentaban cicatrices miocárdicas postisquémicas en el ventrículo izquierdo (VI) y con indicación de cirugía de revascularización miocárdica, se implantaron, durante la operación, células de la médula ósea mononucleares autólogas (CMO) en la cicatriz. Se agregó sobre esa zona infartada una matriz de colágeno tipo I con el mismo número de CMO

Resultados. No hubo mortalidad ni eventos adversos relacionados (seguimiento 15±4,2 meses). La clase funcional según la New York Heart Association (NYHA) mejoró de 2,3±0,5 a 1,4±0,3 (p=0,005). El volumen de fin de diástole del VI evolucionó de 142±24 a 117±21 mL (p=0,03), el tiempo de desaceleración del llenado del VI mejoró aumentando de 162±7 mseg a 196±8 mseg (p=0,01). El espesor del área cicatrizada progresó de 6±1,4 a 9±1,5 mm (p=0,005). La fracción de eyección (FE) mejoró de 25±7 a 33±5% (p=0,04).Conclusiones. La inyección intramiocárdica de células de médula ósea y la fijación simultánea de una matriz sembrada con progenitores celulares (stem cells) sobre el epicardio fue simple y sin complicaciones. La matriz de colágeno aumento el espesor de la zona del infarto con nuevos tejidos viables, limitando la dilatación ventricular y mejorando la función diastólica. Estos resultados positivos no pueden ser absolutamente relacionados a las células y la matriz, pues se asociaron puentes de revascularización coronaria. En conclusión, la ingeniería de tejidos puede extender las indicaciones y beneficios de la terapia con células madre en cardiología, convirtiéndose en un camino prometedor para la creación de un “miocardio bioartificial”

Objectives. Stem cell therapy for myocardial regeneration is limited by poor graft viability and low cell retention. In ischemic cardiomyopathy the extracellular matrix is pathologically modified, therefore it could be important to associate a procedure aiming at regenerating both, myocardial cells and the extracellular matrix. We evaluated intrainfarct cell therapy associated with a cell-seeded collagen scaffold grafted onto infarcted hearts.Methods. In 15 patients (aged 54.2±3.8 years) presenting LV postischemic myocardial scars and with indication for a single off-pump-CABG, autologous mononuclear bone marrow cells (BMC) were implanted during surgery in the scar. A 3D collagen type I matrix seeded with the same number of BMC was grafted onto the infarction zone.Results. There was no mortality and any related adverse events (follow-up 15±4.2 months). NYHA FC improved from 2.3±0.5 to 1.4±0.3 (p=0.005). LV end-diastolic volume evolved from 142±24 to 117±21 mL (p=0.03), LV filling deceleration time improved from 162±7 ms to 196±8 ms (p=0.01). Scar area thickness progress from 6±1.4 to 9±1.5mm (p=0.005). EF improved from 25±7 to 33±5% (p=0.04).Conclusions. Simultaneous intramyocardial injection of mononuclear bone marrow cells and fixation of a BMC-seeded matrix onto the epicardium is feasible and safe. The cell seeded collagen matrix seems to increase the thickness of the infarct scar with viable tissues and help to normalize cardiac wall stress in injured regions, thus limiting ventricular remodelling and improving diastolic function. Patients’ improvements can not be conclusively related to the cells and matrix due to the association of CABG. Cardiac tissue engineering should extend the indications and benefits of stem cell therapy in cardiology, becoming a promising way for the creation of a “bioartificial myocardium”

Effects of Tongxinluo-facilitated cellular cardiomyoplasty with autologous bone marrow-mesenchymal stem cells on postinfarct swine hearts / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion.</p><p><b>METHODS</b>Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n = 7); group 2, administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n = 7); group 3, MSCs alone (n = 7) and group 4, TXL + MSCs (n = 7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3 x 10(7) cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint.</p><p><b>RESULTS</b>At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P < 0.0001); the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone (P < 0.0001) and the peri-infarct zone (P < 0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group (P < 0.0001). SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P < 0.0001). TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase (SOD) significantly increased and malondialdehyde (MDA) decreased in groups 2 and 4 by the administration of TXL.</p><p><b>CONCLUSIONS</b>Our study demonstrates the following: (1) immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; (2) TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.</p>

Transplante celular: nova perspectiva para o tratamento da insuficiência cardíaca / Cell transplantation: a new perspective to heart failure treatment

A despeito da expectativa de alguns autores, o tratamento convencional da insuficiência cardíaca não proporciona regeneração miocárdica. Para isso, o transplante celular ou cardiomioplastia celular poderia representar nova opção de tratamento da insuficiência cardíaca e doença coronária. Células transplantadas em área isquêmica, bem como em cicatrizes de infarto prévio, melhoram a disfunção miocárdica. São necessários novos trabalhos para confirmar esses resultados, entretanto, os resultados disponíveis são promissores. O futuro próximo sinaliza como terapêutica a reconstrução do miocárdio lesado por replicação de cardiomiócitos, transplante ou ativação de células-tronco. O implante local de células da medula óssea autóloga induz angiogênese e melhora áreas isquémicas do miocardio, prevenindo o remodelamento ventricular e melhorando a função cardíaca.

Transformation of Adult Mesenchymal Stem Cells into Cardiomyocytes with 5-azacytidine: Isolated from the Adipose Tissues of Rat / 대한흉부외과학회지

BACKGROUND: Loss of cardiomyocytes in the myocardial infarction leads to regional contractile dysfunction, and necrotized cardiomyocytes in infracted ventricular tissues are progressively replaced by fibroblasts forming scar tissue. Although cardiomyoplasty, or implantation of ventricular assist device or artificial heart was tried in refractory heart failure, the cardiac transplantation was the only therapeutic modality because these other therapeutic strategies were not permanent. Cell transplantation is tried instead of cardiac transplantation, especially bone marrow is the most popular donated organ. But because bone marrow aspiration procedure is invasive and painful, and it had the fewer amounts of cellular population, the adipose tissue is recommended for harvesting of mesenchymal stem cells. MATERIAL AND METHOD: After adipose tissues were extracted from abdominal subcutaneous adipose tissue and intra-abdominal adipose tissue individually, the cellular components were obtained by same method. These cellular components were tried to transformation with the various titers of 5-azacytidine to descript the appropriate concentration of 5-azacytidine and possibility of transformation ability of adipose tissue. Group 1 is abdominal subcutaneous adipose tissue and Group 2 is intra-abdominal adipose tissue-retroperitoneal adipose tissue and omentum. Cellular components were extracted by collagenase and NH4Cl et al, and these components were cultured by non-induction media-DMEM media containing 10% FBS and inducted by none, 3 micromol/L, 6 micromol/L, and 9 micromol/L 5-azacytidine after the 1st and 2nd subculture. After 4 weeks incubation, the cell blocks were made, immunostaining was done with the antibodies of CD34, heavy myosin chain, troponin T, and SMA. RESULT: Immunostaining of the transformed cells for troponin T was positive in the 6 micromol/L & 9 micromol/L 5-azacytidine of Group 1 & 2, but CD34 and heavy myosin chain antibodies were negative and SMA antibody was positive in the 3 micromol/L & 6 micromol/L 5-azacytidne of Group 2. CONCLUSION: These observations confirm that adult mesenchymal stem cells isolated from the abdominal subcutaneous adipose tissues and intra-abdominal adipose tissues can be chemically transformed into cardiomyocytes. This can potentially be a source of autologous cells for myocardial repair.

Use what you have--biological assistance for the treatment of heart failure in the Caribbean

Cardiovascular disease represents the main cause of death among adults in the Caribbean. Primary and secondary care facilities are efficiently managed. Cardiac surgical and interventional facilities, however, exist only in a small number of territories and are mainly privately funded and are only accessible to few patients. Patients with end-stage heart failure (ESHF) are given few options apart from palliative care or to seek treatment outside of the region. Transplantation remains the 'gold standard' therapy for ESHF. Establishing a Caribbean cardiac transplantation programme would require legislative and infrastructure changes. Tissue rejection poses a problem and expensive immunosuppressants are needed. Mechanical assist devices are costly and associated with complications such as haemorrhage, thrombosis and infections. Both forms of therapy require significant technical and financial investment and do not appear to be economically viable for the Caribbean. The use of the patient's own skeletal muscle to perform biological cardiac assistance is potentially the ideal alternative. The skeletal muscle is conditioned by electrical stimulation to become fatigue resistant. It is then transposed and harnessed as an auxilliary circulatory pump. The required muscle stimulators are relatively inexpensive and the surgical techniques and postoperative care are not overly demanding. We discuss the financial and research implications of treating patients from the Caribbean who have end-stage heart failure

Implante intracoronario de células progenitoras de la médula ósea en disfunción ventricular posinfarto por lupus eritematoso sistémico / Intracoronary implant of autologous progenitor cells of bone marrow in ventricular disfunction postinfarct by systemic lupus erythematosus

El caso que se presenta, trata de una paciente con diagnóstico de miocardiopatía isquémica necrótica por lupus eritematoso sistémico con infarto anterolateroapical evolucionado. Por cateterismo intracoronario se implanta, en esta zona muerta, una solución autóloga de médula ósea enriquecida con células progenitoras CD34+. En el seguimiento a los tres meses pudimos comparar restauración de viabilidad en los segmentos comprometidos.

Opções cirúrgicas no tratamento da insuficiência cardíaca / Surgical alternatives for the treatment of patients in refractory heart failure

Apesar do aprimoramento da terapêutica clínica, alguns pacientes com insuficiência cardíaca atingem classe funcional IV refratária. Nessa situação, pode ser necessário tratamento cirúrgico, que deverá ser individualizado. Os pacientes com coronariopatia e déficit ventricular importante podem ter melhora da função ventricular e da classe funcional se factível a revascularização do miocárdio (leito coronariano adequado). Lembrar do tratamento do aneurisma ventricular quando presente. A cardiomioplastia (retalho muscular pediculado envolvendo e contraindo sincronicamente com o coração por marcapasso) pode melhorar a classe funcional a curto prazo, porém tem sido observada degeneração do músculo estriado a longo prazo. A ventriculectomia parcial (ressecção de parte do ventrículo esquerdo) tem ressurgido, embora abordando principalmente áreas fibróticas ou acinéticas, associada a outros procedimentos. A remodelação ventricular esquerda associada à correção da insuficiência mitral tem tido bons resultados, com melhora funcional e boa sobrevida a longo prazo em doentes com miocardiopatia dilatada com regurgitação mitral secundária. Em pacientes com QRS largo, a ressincronização das câmaras cardíacas com marcapasso biventricular é medida pouco invasiva, que oferece melhora da fração de ejeção e da classe funcional e pode reduzir a insuficiência mitral. Os desfibriladores implantáveis têm indicação nos pacientes que já foram reanimados após arritmias ventriculares malignas, mas não mudam a evolução da insuficiência cardíaca. O transplante cardíaco ainda é o tratamento de eleição para a insuficiência cardíaca classes funcionais III e IV, porque, apesar de risco de infecções e episódios de rejeição, esses pacientes têm sobrevida superior a 80 por cento no primeiro ano e superior a 65 por cento no quinto ano pós-transplante, com excelente qualidade de vida (classe funcional I).

Studies on Differentiation of Cardiac Myoblast Induced by Co-culture with Isolated Neonatal Rat Cardiac Myocytes / 대한해부학회지

Cellular cardiomyoplasty has recently emerged as a potential new treatment of ischemic heart disease. Combining cellular cardiomyoplasty with gene therapy using myogenic transcription factor might facilitate myocardial regeneration. In this study, we engineered H9c2, L6 using plasmid vector to overexpress the transcription factor MEF2c, Nkx2.5 involved in cardiomyogenesis. We investigated 1) formation of intercellular junction in mono-culture and co-culture with cardiomyocyte for functional and structural synchronous contraction after transplantation, 2) differentiation into cardiomyocyte, 3) resistance to hypoxic condition. Each cell overexpressing MEF2 and Nkx2.5 was generated by gene transfection and clonal selection. CO-culture was performed that each cell line added over cultured cardiomyocyte. H9c2-MEF2c and H9c2-Nkx2.5 became long, spindle shape like cardiomyocyte. Troponin T, cardiac specific marker, was found spot-like pattern in H9c2-Nkx2.5. However, co-culture with cardiomyocyte did not induce differentiation all kinds of cells into cardiomyocyte. Connexin43, which is gap junction marker was increased in H9c2-MEF2c, H9c2-Nkx2.5, L6-MEF2c and L6-Nkx2.5. Especially, co-culture with cardiomyocyte resulted in elevation of connexin43 levels more than monoculture. Ultrastructurally, formations of gap junction and desmosome were found apparently in L6-Nkx2.5. Long-standing, strong, regular and more frequent contraction were observed in cardiomyocyte co-cultured with H9c2-MEF2c, H9c2-Nkx2.5, L6-MEF2c, L6-Nkx2.5, respectively. Neverthless, any cell did not have active contraction itself, but passive movement except cardiomyocyte. H9c2-MEF2c, L6-MEF2c and L6-Nkx2.5 had resistance to hypoxia compared with other groups. These results suggested that co-culture and overexpressions of MEF2c and Nkx2.5 induced differentiation into cardiomyocyte and played an important role on intercellular junction formation and hypoxic resistance. This would be a promising source of cellular cardiomyoplasty. Therefore, much more research would be essential for clinical application of cellular cardiomyoplasty and this study would be a basic source for further study of MEF2c and Nkx2.5 in cellular cardiomyoplasty.

Role of Cardiac Transcription Factor Nkx2.5 on Cardiomyoplasty Model in vitro / 대한해부학회지

Despite therapeutic advance, the prevalence of ischemic heart disease continues to increase. Recently, cell transplantation of stem cell has been proposed as a strategy for cardiac repair following myocardial damage. However, low differentiation efficiency into cardiomyocyte and poor cell viability associated with transplantation have limited the reparative capacity of these cell. In this study, we engineered P19 embryonal carcinoma cells using plasmid vector to overexpress the transcription factor MEF2c, Nkx2.5 involved in cardiomyogenesis. We investigated 1) formation of intercellular junction of P19 in mono-culture and co-culture with cardiomyocyte for functional and structural synchronous contraction after transplantation, 2) differentiation into cardiomyocyte, 3) resistance to hypoxic condition. An P19 embryonal carcinoma cell line expressing GFP, MEF2c, Nkx2.5 was generated by gene transfection and clonal selection. Nkx2.5 overexpression induced connexin43 expression level decrease. Electron microscopy revealed myofibril organization and immunostaining with cTnT showed positive staining in P19-Nkx2.5, consistent with early stage cardiomyocyte. Connexin43 and N-cadherin was expressed between P19-MEF2c and cardiomyocyte, P19- Nkx2.5 and cardiomyocyte in co-culture. And beating rate of cardiomyocyte co-cultured with P19-Nkx2.5 increased much more than other group, even if P19-Nkx2.5 did not have synchronous contraction with cardiomyocyte. Additionally, P19-Nkx2.5 had a resistance against hypoxia. These result suggest that overexpression of Nkx2.5 induced differentiation of P19 into cardiomyocyte and would be electro-mechanical coupling with cardiomyocyte after transplantation. Futhermore, Nkx2.5 overexpression had protection potential to hypoxic injury. Therefore, P19 cell overexpressed Nkx2.5 would be promising cell source for further study of new therapy of myocardial disease and building up in vitro model.

Cellular Cardiomyoplasty Using Bone Marrow Derived Mesenchymal Stem Cells Transplantation in Post Myocardial Infarction Heart Failure

BACKGROUND AND OBJECTIVES: Cellular cardiomyoplasty (CCM) is considered to be a novel therapeutic approach for post-myocardial infarction (MI) heart failure. In this study, the functional effects of cultured mesenchymal stem cells (MSCs) transplantation and the associated histopathologic changes were evaluated in a rat model of MI. MATERIALS AND METHODS: Rats were subjected to 5 hours of coronary ligation followed by reperfusion, and 10 days after MI, animals were randomized into either the MSCs transplantation (MI-MSC, n=8) group or the control (n=8) group. Allogeneic MSCs (3x10(6) cells) or media were epicardially injected into the center and the border area of the infarct scar. RESULTS: Four weeks after the MSCs transplantation, the echocardiogram showed preserved anterior regional wall motion and increases in fractional shortening in the MI-MSC heart relative to the control heart. Left ventricular (LV) end diastolic pressure was smaller in the MI-MSC than in the control group. Implanted MSCs formed islands of cell clusters on the border of the infarct scar, and the cells were positively immunostained by sarcomeric alpha-actinin and cardiac troponin T. In addition, the number of microvessels on the border area of the infarct scar was greater in the MI-MSC than in the control group. CONCLUSION: Allogeneic MSCs transplanted into the MI scar formed clusters of cell grafts on the border of the infarct, expressed cardiac muscle proteins, increased microvessel formation, and improved regional and global LV function. Our data indicate that CCM using MSCs may have a significant role in the treatment of post-MI heart failure.

Partial left ventriculectomy: a retrospective study

OBJETIVO: Este estudo foi empreendido para identificar fatores que poderiam ter contribuído para o decréscimo da mortalidade e da morbidade em pacientes submetidos a ventriculectomia parcial esquerda (VPE) pela análise de dados descritores de resultados acumulados, a partir de diferentes publicaçäes seqüenciais, entre 1995 e 1998. MÉTODO: Dados clínicos rotineiros, envolvendo aspectos cirúrgicos e resultados pós-operatórios, foram reunidos e, quando possível, selecionados para análise comparativa. RESULTADOS: A VPE foi capaz de possibilitar uma melhora muito significativa no desempenho da função sistólica e da qualidade de vida dos sobreviventes livres de eventos, mas também pode ser claramente verificado que, numa importante proporção destes sobreviventes ù como uma seqüência evolutiva ù a VPE foi incapaz de modificar a tendência das fibras miocárdicas de retornar ao modelo do pré-operatório, na evolução tardia. Além disso, o diâmetro diastólico final ù ecocardiograficamente avaliado ù de 7,5 cm (ñ1,4 cm) foi o suporte quantitativo mais significativo para a indicação da VPE, em uma coorte de 465 pacientes de dois a 74 anos de idade. Em uma sucessão de resultados individuais nos quais a mortalidade pós-operatória oscilou de 0 a 60 por cento, a sobrevivência à VPE mostrou relação significativa com a evolução da morfologia da célula miocárdica no pós-operatório e aumentou exponencialmente, em termos absolutos, quando pacientes com aumento persistente da disfunção ventricular foram tratados com dispositivo de assistência ao ventrículo esquerdo. Left Ventricular Assist Device (LVAD). CONCLUSAO: A impossibilidade material de identificar preditores qualificados das chances de evolução pós-operatórias emergiu como uma limitação crucial para o uso rotineiro da reversão cirúrgica da dilatação da cavidade ventricular para tratar cardiomiopatias dilatadas, a despeito da experiência e dos valores numéricos acumulados.

Risk factors of mortality in nine years of follow-up after dynamic cardiomyoplasty

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