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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. [ABSTRACT FROM AUTHOR]

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.

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 fastand 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cell replacement in the heart is considered a promising strategy for the treatment of post-infarct heart failure. Direct intramyocardial injection of cells proved to be the most effective application route, however, engraftment rates are very low (<5%) strongly hampering its efficacy. Herein we combine magnetic nanoparticle (MNP) loading of EGFP labeled embryonic cardiomyocytes (eCM) and embryonic stem cell-derived cardiomyocytes (ES-CM) with application of custom designed magnets to enhance their short and long-term engraftment. To optimize cellular MNP uptake and magnetic force within the infarct area, first numerical simulations and experiments were performed in vitro . All tested cell types could be loaded efficiently with SOMag5-MNP (200 pg/cell) without toxic side effects. Application of a 1.3 T magnet at 5 mm distance from the heart for 10 min enhanced engraftment of both eCM and ES-CM by approximately 7 fold at 2 weeks and 3.4 fold (eCM) at 8 weeks after treatment respectively and also strongly improved left ventricular function at all time points. As underlying mechanisms we found that application of the magnetic field prevented the initial dramatic loss of cells via the injection channel. In addition, grafted eCM displayed higher proliferation and lower apoptosis rates. Electron microscopy revealed better differentiation of engrafted eCM, formation of cell to cell contacts and more physiological matrix formation in magnet-treated grafts. These results were corroborated by gene expression data. Thus, combination of MNP-loaded cells and magnet-application strongly increases long-term engraftment of cells addressing a major shortcoming of cardiomyoplasty. [ABSTRACT FROM AUTHOR]

Objective: Extracorporeal membrane oxygenation (ECMO) is used to provide cardiorespiratory support during cardiopulmonary resuscitation (extracorporeal cardiopulmonary resuscitation; ECPR) unresponsive to conventional methods. In this study, the results of ECPR in a cardiac arrest setting after cardiac surgery in children were analyzed. Methods: In this retrospective cohort study, between November 2010 and June 2014, 613 congenital heart operations were performed by the same surgical team. Medical records of all the patients who experienced cardiac arrest and ECPR in an early postoperative period (n=25; 4%) were analyzed. Their ages were between 2 days and 4.5 years (median: 3 months). Sixteen patients had palliative procedures. In 88% of the patients, cardiac arrest episodes occurred in the first 24 h after operation. Mechanical support was provided by cardiopulmonary bypass only (n=10) or by ECMO (n=15) during CPR. Results: The CPR duration until commencing mechanical support was <20 min in two patients, 20-40 min in 11 patients, and >40 min in 12 patients. Eleven patients (44%) were weaned successfully from ECMO and survived more than 7 days. Five of them (20%) could be discharged. The CPR duration before ECMO (p=0.01) and biventricular physiology (p=0.022) was the key factor affecting survival. The follow-up duration was a mean of 15±11.9 months. While four patients were observed to have normal neuromotor development, one patient died of cerebral bleeding 6 months after discharge. Conclusion: Postoperative cardiac arrest usually occurs in the first 24 h after operation. ECPR provides a second chance for survival in children who have had cardiac arrest. Shortening the duration of CPR before ECMO might increase survival rates. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to report the preliminary experience with the techniques and utility of navigation-guided, 3D, computed tomography-dacryocystography (CT-DCG) in the management of secondary acquired lacrimal drainage obstructions. Methods: Stereotactic surgeries using CT-DCG as the intraoperative image-guiding tool were performed in 3 patients. One patient had nasolacrimal duct obstruction (NLDO) following a complete maxillectomy for a sinus malignancy, and the other 2 had NLDO following extensive maxillofacial trauma. All patients underwent a 3D CT-DCG. Image-guided dacryolocalization (IGDL) was performed using the intraoperative image-guided StealthStation™ system in the electromagnetic mode. All patients underwent navigation-guided powered endoscopic dacryocystorhinostomy (DCR). The utility of intraoperative dacryocystographic guidance and the ability to localize the lacrimal drainage system in the altered endoscopic anatomical milieu were noted. Results: Intraoperative geometric localization of the lacrimal sac and the nasolacrimal duct could be easily achieved. Constant orientation of the lacrimal drainage system was possible while navigating in the vicinity of altered endoscopic perilacrimal anatomy. Useful clues with regard to modifications while performing a powered endoscopic DCR could be obtained. Surgeries could be performed with utmost safety and precision, thereby avoiding complications. Detailed preoperative 3D CT-DCG reconstructions with constant intraoperative dacryolocalization were found to be essential for successful outcomes. Conclusion: The 3D CT-DCG-guided navigation procedure is very useful while performing endoscopic DCRs in cases of secondary acquired and complex NLDOs. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the leading cause of death in industrialized nations. Due to the high number of patients and expensive treatments, according to the Federal Statistical Office (2017) in Germany, cardiovascular diseases account for around 15% of total health costs. Advanced coronary artery disease is mainly the result of chronic disorders such as high blood pressure, diabetes, and dyslipidemia. In the modern obesogenic environment, many people are at greater risk of being overweight or obese. The hemodynamic load on the heart is influenced by extreme obesity, which often leads to myocardial infarction (MI), cardiac arrhythmias, and heart failure. In addition, obesity leads to a chronic inflammatory state and negatively affects the wound-healing process. It has been known for many years that lifestyle interventions such as exercise, healthy nutrition, and smoking cessation drastically reduce cardiovascular risk and have a preventive effect against disorders in the healing process. However, little is known about the underlying mechanisms, and there is significantly less high-quality evidence compared to pharmacological intervention studies. Due to the immense potential of prevention in heart research, the cardiologic societies are calling for research work to be intensified, from basic understanding to clinical application. The topicality and high relevance of this research area are also evident from the fact that in March 2018, a one-week conference on this topic with contributions from top international scientists took place as part of the renowned "Keystone Symposia" ("New Insights into the Biology of Exercise"). Consistent with the link between obesity, exercise, and cardiovascular disease, this review attempts to draw lessons from stem-cell transplantation and preventive exercise. The application of state-of-the-art techniques for transcriptome analysis has opened new avenues for tailoring targeted interventions to very individual risk factors.

Objectives: The aim was to create a model of myocardial infarction with a borderline myocardial impairment which would enable evaluation of the retrograde cellular cardiomyoplasty through the venous coronary sinus in a large animal model.Materials and Methods: Fifteen (study group) and 10 juvenile farm pigs (control group) underwent distal left anterior descending artery ligation. One month later the study group animals underwent sternotomy and a murine myoblastic line C2-C12 was injected at a constant pressure of 30mmHg, into the coronary sinus. Thirty days later all animals that survived from both groups underwent transthoracic echocardiography and 99Tc scintigraphy and were later euthanized and specimens were taken for microscopic evaluation.Results: Cardiac output decreased significantly after ligation (p<0.001) and increased significantly after cardiomyoplasty (p<0.001). In all animals, the surgical induction of myocardial infarction caused a marked decline in the echocardiographic values of cardiac function; however, the cardiac function and dimensions were significantly improved in the study group after cardiomyoplasty versus the control group. All animals undergoing cardiomyoplasty demonstrated a significant reduction of the perfusion deficit in the left anterior descending artery territory, instead such data remained unchanged in the control group. The histological examination demonstrated the engrafted myoblasts could be distinguished from the activated fibroblasts in the scar tissue because they never showed any signs of collagen secretion and fiber buildup.Conclusions: In conclusion, the venous retrograde delivery route through the coronary sinus is safe and effective, providing a significant improvement in function and viability. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine whether there remain developmental differences between term infants at 3 years of age following major non-cardiac surgery (NCS) and cardiac surgery (CS) compared with healthy control infants in New South Wales (NSW), Australia.Study Design: Between 2006 and 2008, term infants who required NCS or CS within the first ninety days of life were enrolled in a prospective population-based study. Their developmental outcome was then compared with a cohort of healthy term infants. Infants initially assessed at 1 year of age were then re-assessed at 3 years of age using the Bayley scales of infant and toddler development (version-Iii) Results: Of the 539 term infants assessed at 1 year of age, 417 returned for the 3-year assessment, with 378 complete assessments. The mean scores for the infants who underwent CS (P < 0.001) were significantly lower in all subscales of the assessment compared with the controls, while the mean scores for the infants who underwent NCS were significantly lower in three of the subscales (P < 0.05). The infants who underwent CS scored significantly lower in four of the subscales (P < 0.05), compared with the infants who underwent NCS.Conclusion: The second phase of this unique population-based study provides further data on the outcomes of infants who underwent major NCS and CS. Major surgery in infants continues to be associated with developmental delay at 3 years of age compared with control infants; however the majority of the delay is mild. The risk remains higher in CS group with the pattern and severity of delay similar to that observed in the first study. [ABSTRACT FROM AUTHOR]

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.

The functional coupling of transplanted cells with host myocardial cells is a significant challenge in mesenchymal stem cell (MSC) cardiomyoplasty being related to cell survival and therapeutic outcomes. Priming of MSCs with growth factors has been reported to improve their therapeutic efficacy through gap junction-mediated mechanisms. However, the expression pattern of Connexin43 (Cx43) in growth factor-stimulated MSC was not previously addressed. In this study we investigated how the pre-treatment with growth factors modulates MSC ability to integrate into the host tissue after transplantation, with particular focus on the expression of Cx43 and its cellular distribution. Our results showed that stimulation of MSCs with IGF-1, FGF-2, but not TGFβ, increased the level of Cx43 at both mRNA and protein levels. IGF-1 stimulation resulted in a shift of the fibroblast morphology into an epithelial morphology in several well-defined areas of stimulated cells. Confocal microscopy examination revealed that the increase of Cx43 was restricted to the epithelial-like cells and did not occur in other cells. In variance, FGF-2 induced a rod-shape morphology of every single cell, which achieved an extremely low cell index. FGF-2 stimulation also induced a time-dependent increase in Cx43, with a regular distribution pattern in all cells. Dye transfer assay coupled with confocal microscopy and flow cytometry analysis demonstrated functional in vitro cell coupling between FGF-2-stimulated MSCs as well as between FGF-2-stimulated cells and H9c2 cardiomyoblasts, a scenery that mimick MSC transplantation into the myocardium. We conclude that the stimulation of MSCs with FGF-2 prior to transplantation may facilitate their access among the myocardial cells and increase the functional coupling between transplanted and host cells. [ABSTRACT FROM AUTHOR]

Stem cell-based therapies are considered to be promising and innovative therapeutic strategies for heart repair. Patient-derived induced pluripotent stem cells (iPSCs) are now available, which combine the advantages of autologous adult stem cells with the unlimited potential of embryonic stem cells for proliferation and differentiation. Intense research has driven dramatic progress in various areas of iPSC technology relevant for clinically applicable iPSC-based cellular therapies. At this point, it is already possible to generate transgene-free autologous iPSCs from small blood samples or hair, to scale up the expansion and differentiation of iPSCs to clinically required dimensions, and to obtain highly enriched cardiomyocyte preparations. On the other hand, critical hurdles such as the targeted specification of distinct cardiomyocyte subpopulations, survival and proper functional integration of cellular transplants after myocardial infarction, and in vitro engineering of prevascularized muscle patches have yet to be overcome. Nevertheless, concepts of cellular cardiomyoplasty seem to have come of age and the first clinical applications of iPSC-based heart repair can be expected within the coming years. [ABSTRACT FROM AUTHOR]

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.

Perioperative management of patients after percutaneous coronary intervention presents physicians with unique challenges and dilemmas. Although newer generation drug-eluting stents, transcatheter-based therapies, and minimally invasive surgical techniques have changed the medical landscape, guidelines for managing perioperative patients after percutaneous intervention are based largely on expert opinion and inconsistent data from an earlier era. In conclusion, the aims of this review are to summarize the data pertinent to managing patients after percutaneous coronary intervention in the perioperative period and to explore future perspectives. [ABSTRACT FROM AUTHOR]

Aims Survivors of out-of-hospital cardiac arrest (OHCA) have a high rate of morbidity and mortality. Invasive cardiac assessment with coronary angiography offers the potential for improving outcomes by facilitating early revascularization. The aim of the present study was to review the published data on early coronary angiography for survivors of OHCA, and its impact on survival and neurological outcomes. Methods Medline, Embase and PubMed were searched with a structured search query. The primary outcome was in-hospital (or if not available, 30 day or 6 month) survival. Rates of survival with good neurological outcome were a secondary endpoint. The time period of the search was from 1 January 1980 to 1 January 2014. Data was pooled with means and 95% CI interval calculated. Meta-analysis of the main outcomes was performed using a weighted random effects model. Results Following review of all identified records, 105 relevant full text articles were retrieved. Fifty had adequate outcome information stratified by the use of coronary angiography for analysis. In studies where a control group was available for comparison, the overall survival in the acute angiography group was 58.8% versus 30.9% in the control group (Odds ratio 2.77, 95% CI 2.06–3.72). Survival with good neurological outcome (as per the Utstein framework) in the early angiography group was 58% versus 35.8% in the control group (Odds ratio 2.20, 95% CI 1.46–3.32). Conclusions Early coronary angiography in patients following OHCA is associated with improved outcome and better survival. [ABSTRACT FROM AUTHOR]

Surgical anxiety creates psychological and physiological stress, causes complications in surgical procedures, and prolongs recovery. Relaxation of patients in postoperative intensive care units can moderate patient vital signs and reduce discomfort. This experiment explores the use of virtual reality (VR) cybertherapy to reduce postoperative distress in patients that have recently undergone cardiac surgery. Sixty-seven patients were monitored at IMSS La Raza National Medical Center within 24 hours of cardiac surgery. Patients navigated through a 30 minute VR simulation designed for pain management. Results were analyzed through comparison of pre- and postoperative vital signs and Likert scale survey data. A connection was found in several physiological factors with subjective responses from the Likert scale survey. Heavy positive correlation existed between breathing rate and Likert ratings, and a moderate correlation was found between mean arterial pressure and Likert ratings and heart rate and Likert ratings, all of which indicated lower pain and stress within patients. Further study of these factors resulted in the categorization of patients based upon their vital signs and subjective response, providing a context for the effectiveness of the therapy to specific groups of patients. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is the leading cause of death worldwide. Various therapeutic strategies have been introduced for MI treatment. In recent years, interest in utilizing mesenchymal stem cells (MSCs) for MI therapy has increased. In fact, the use of MSCs for MI treatment, known as cellular cardiomyoplasty, is in the clinical trial stage. However, despite promising results, most MSCs die after transplantation as a result of exposure to various stresses. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a well-known cytoprotective transcription factor, protects MSCs against some stresses. Over-expression of Nrf2 in MSCs decreases their apoptosis in vitro without any adverse effects on their differentiation capacity. Therefore, we hypothesized that over-expression of Nrf2 in MSCs can improve cellular cardiomyoplasty. [ABSTRACT FROM AUTHOR]

Abstract: In this work, the effectiveness of using Gadonanotubes (GNTs) with an external magnetic field to improve retention of transplanted adult mesenchymal stem cells (MSCs) during cellular cardiomyoplasty was evaluated. As a high-performance T1-weighted magnetic resonance imaging (MRI) cell tracking label, the GNTs are gadolinium-loaded carbon nanotube capsules that render MSCs magnetic when internalized. MSCs were internally labeled with either superparamagnetic GNTs or colloidal diamagnetic lutetium (Lu). In vitro cell rolling assays and ex vivo cardiac perfusion experiments qualitatively demonstrated increased magnetic-assisted retention of GNT-labeled MSCs. Subsequent in vivo epicardial cell injections were performed around a 1.3 T NdFeB ring magnet sutured onto the left ventricle of female juvenile pigs (n = 21). Cell dosage, magnet exposure time, and endpoints were varied to evaluate the safety and efficacy of the proposed therapy. Quantification of retained cells in collected tissues by elemental analysis (Gd or Lu) showed that the external magnet helped retain nearly three times more GNT-labeled MSCs than Lu-labeled cells. The sutured magnet was tolerated for up to 168 h; however, an inflammatory response to the magnet was noted after 48 h. These proof-of-concept studies support the feasibility and value of using GNTs as a magnetic nanoparticle facilitator to improve cell retention during cellular cardiomyoplasty. [Copyright &y& Elsevier]

Abstract: Cell-based therapeutic neovascularization is a promising method for treating ischemic disorders. In this work, human umbilical vein endothelial cells (HUVECs) were thoroughly premixed with cord-blood mesenchymal stem cells (cbMSCs) and cultivated to form three-dimensional (3D) cell aggregates for cellular cardiomyoplasty. In the in vitro study, tubular networks were formed at day 1 after the co-culturing of dissociated HUVECs and cbMSCs on Matrigel; however, as time progressed, the grown tubular networks regressed severely. Conversely, when 3D cell aggregates were grown on Matrigel, mature and stable tubular networks were observed over time, under the influence of their intensive cell–extracellular matrix (ECM) interactions and cell–cell contacts. 3D cell aggregates were transplanted into the peri-infarct zones of rats with myocardial infarction (MI) via direct intramyocardial injection. Based on our pinhole single photon emission computed tomography (SPECT) myocardial-perfusion observations, echocardiographic heart-function examinations and histological analyses, the engrafted 3D cell aggregates considerably enhanced the vascular densities and the blood flow recovery in the ischemic myocardium over those of their dissociated counterparts, thereby reducing the size of perfusion defects and restoring cardiac function. These results demonstrate that the intramuscular delivery of 3D cell aggregates of HUVECs/cbMSCs can be a valuable cell-based regenerative therapeutic strategy against MI. [Copyright &y& Elsevier]

The association of stem cells with tissue-engineered scaffolds constitutes an attractive approach for the repair of myocardial tissue with positive effects to avoid ventricular chamber dilatation, which changes from a natural elliptical to spherical shape in heart failure patients. Biohybrid scaffolds using nanomaterials combined with stem cells emerge as new therapeutic tool for the creation of 'bioartificial myocardium' and 'cardiac wrap bioprostheses' for myocardial regeneration and ventricular support. Biohybrids are created introducing stem cells and self-assembling peptide nanofibers inside a porous elastomeric membrane, forming cell niches. Our studies lead to the creation of semi-degradable 'ventricular support bioprostheses' for adaptative LV and/or RV wrapping, designed with the concept of 'helical myocardial bands'. The goal is to restore LV elliptical shape, and contribute to systolic contraction and diastolic filling (suction mechanism). Cardiac wrapping with ventricular bioprostheses may reduce the risk of heart failure progression and the indication for heart transplantation. [ABSTRACT FROM AUTHOR]