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Objectives Myocardial autophagy has been recognized as an important factor in heart failure. It is not known whether changes in ventricular geometry by left ventriculoplasty influence autophagy in ischemic cardiomyopathy. We hypothesized that myocardial autophagy plays an important role in left ventricular (LV) redilation after ventriculoplasty. Methods Four weeks after ligation of the left anterior descending artery, ventriculoplasty or sham operation was performed. The animals were euthanized at 2 days (early) or 28 days (late) after the second operation. Ventricular autophagy was evaluated by protein expression of microtubule-associated protein light chain 3 II, an autophagosome marker. Cardiomyocyte area was assessed by histologic examination. LV function was evaluated by echocardiography. To examine the implications of autophagy, an autophagy inhibitor (3-methyladenine) was injected intraperitoneally for 3 weeks before sacrifice. Results The LV was reduced in size early and redilated late after ventriculoplasty. LV systolic function was improved early and later worsened after ventriculoplasty. Light chain 3 II expression decreased early after ventriculoplasty and increased in the late period. Myocyte area increased from the early to late stage after ventriculoplasty. Autophagic inhibition exaggerated the increased myocyte hypertrophy and LV redilation. Conclusions In a rat model of myocardial infarction, autophagy decreased early after ventriculoplasty and increased again during LV redilation. These results provide new insights into the mechanism underlying the late failure of ventriculoplasty.

Objective. Improvement of the treatment results in patients with refractory angina, complicated by the heart insufficiency, using new methods of correction of the heart pumping function elaborated. Materials and methods. Clinical investigation was performed, basing on retro- and prospective analysis of the treatment results in 156 patients: efficacy of myocardial remodeling was studied, using mesenchymal stem cells in patients, suffering refractory angina. For determination of the cellular therapy efficacy a navigation system NOGA XP was applied. Results. There were presented the results of investigation of efficacy of intravenous injections of autologous mesenchymal stem cells to patients, suffering refractory angina, complicated by lowering of the heart pumping function, and immediate results of cardiomyoplasty using stem cells as well. For the first time a navigation system NOGA XP for determination of myocardial hibernation zones was applied in patients, suffering refractory angina. Also, using navigation system NOGA XP, the results of cellular cardiomyoplasty were obtained, while comparing electro-mechanical schemes before and after cellular therapy. Conclusion. There was established the improvement of indices of the heart pumping function and the patients’ quality of life.

Heart disease is one of the leading causes of morbidity and mortality worldwide. Two of these diseases are heart failure and myocardial infarction. In America alone, there are about 6.2 million people with heart failure, and every 40 seconds, a patient with a heart attack is recorded. Myocardial infarction, known as a heart attack, occurs after the blocking or occlusion of a coronary artery, disabling the delivery of oxygenated blood to regions of the heart. Heart failure, usually occurring after ischemic diseases like myocardial infarction, is where the heart loses the ability to pump a sufficient blood supply to meet the body’s needs. The major ways of treating heart failure and myocardial infarction today are either too expensive or hard to come by, so a new sort of treatment is direly needed. Cellular cardiomyoplasty, a form of cell therapy, is being looked into as a new way to treat these two and other cardiomyopathies. Additionally, though there have been a few cells that have shown a possibility of use for cardiomyoplasty, this review focuses on mesenchymal stem cells, specifically called mesenchymal stromal cells. The purpose of this review is to look into what cellular cardiomyoplasty is, how it may be used in the future, and how mesenchymal stromal cells have shown potential to be used for it.

Modern advances in the medical and surgical treatment of coronary heart disease (CHD), unfortunately, will not solve the entire arsenal of problems, associated with impaired microcirculatory myocardial perfusion. The proposed methods of influence on microvascular dysfunction of the ischemic myocardium, including cell cardiomyoplasty and laser myocardial tunneling, include a relatively short-lasting positive effect. For a more successful application of these modern approaches, an increase in the compensatory-reparative capabilities in these patients plays a significant role. A positive result of treatment, in this case, can be achieved by applying pre- and postoperative immunocorrection, since all these processes are immuno-conditioned.

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.

Background: Observational studies have demonstrated a low prevalence of diabetes mellitus (DM) in patients with takotsubo cardiomyopathy (TCM) and also suggested a possible protective role due to underlying autonomic neuropathy. its impact on TCM outcomes is unclear. Methods: We recruited 8081 patients from 2011, 2012 National Inpatient Sample, 6325 had TCM while 1756 had TCM with DM. Our outcomes of interest were overall mortality, mechanical hemodynamic support (MHS), acute respiratory failure(ARF), cardiac arrest (SCA), cardiogenic shock (CS), and stroke. Logistic regression was used to estimate the adjusted odds ratio of the outcomes in the study compared to the control group while stratified analysis was used to adjust for sex both accounting for underlying comorbidities. Results: The mean age was 60.4 years. There was no difference in overall mortality (4.1% vs 3.5%; P =0.154), cardiogenic shock (6.2% vs 6.2%; P=0.905), atrial fibrillation (11.1 vs 11.8; P= 0.224), stroke (1.9% vs 2.3%; P= 0.139) and MHS (2.3% vs 2.8%; P= 0.086). The rate of acute respiratory failure was significantly higher in DM+TCM patients compared to TCM alone (20.8% vs 18.2%; P= 0.021). Table 1 reveals the adjusted odds ratio for outcomes while table 2 stratified analysis based on age and sex. Patients with TCM+ DM have higher odds for acute respiratory failure and the use of MHS. The stratified analysis revealed that compared to TCM alone, females with TCM +DM are more likely to develop acute respiratory failure, stroke, and the use of MHS, while male patients were more likely to develop atrial fibrillation. Conclusion: Underlying DM is associated with an increased risk for poor outcomes in patients with TCM.

Introduction: Recent studies have demonstrated poor outcomes in patients with takotsubo cardiomyopathy (TCM). It is important to determine the predictors of these outcomes for appropriate risk stratification and to decrease the overall disease burden. Physical stressors and preexisting heart failure have been associated with poorer outcomes, however, the impact of alcohol use (ETOH) has not been discussed. Aim: To determine if underlying alcohol use is associated with poorer outcomes in patients with TCM. Methods: We recruited 6750 patients from 2011, 2012 National Inpatient Sample, 6325 had TCM alone while 425 had TCM and ETOH use. Our outcomes of interest were overall mortality, mechanical hemodynamic support (MHS) acute respiratory failure(ARF), cardiac arrest (SCA), cardiogenic shock, and atrial fibrillation. All clinical characteristics were defined as per the International Classification of Diseases 9th revision (ICD-9) codes. Logistic regression was used to estimate the odds ratio of the outcomes in the study compared to the control group while stratified analysis was used to adjust for age and sex both accounting for underlying comorbidities. Results: There was no significant difference between the two groups in the rates of atrial fibrillation (11.1% vs 10.4%; P= 0.656), cardiogenic shock (6.2% vs 4.7%; P= 0.201), MHS (2.3% vs 1.4%; P= 0.221) and overall mortality (4.1% vs 3.8%; p=0.702). Rates of ARF (29.9%, vs 18.2%; P< 0.0001) and SCA (4.9% vs 3.0%; P=0.025) were higher in patients with TCM+ETOH compared to TCM alone. Table 1 displays the adjusted odds ratios for the outcomes. Compared to the participants with TCM alone, odd ratios of ARF was significantly higher in patients with TCM+ETOH. Table 2 displays the stratified analysis based sex. Compared with TCM alone, female patients with TCM+ETOH are more likely to develop ARF, cardiogenic shock and SCA. Conclusion: Preexisting alcohol use is associated with poorer outcomes in female patients with TCM.

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.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.Cardiac output decreased significantly after ligation (p0.001) and increased significantly after cardiomyoplasty (p0.001). 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.In conclusion, the venous retrograde delivery route through the coronary sinus is safe and effective, providing a significant improvement in function and viability.

Introduction Current experimental research has proven the efficacy of transplantation bone marrow-derived mesenchymal stem cells (MSC) in the treatment of myocardial infarction (MI). The one of the main purposes of research was to evaluate the comparative data of the MSC transplantation with (5-azacytidine) and without commitment and to assess the post transplantation effects. Methods The efficiency of intravenous cardiomyoplasty by infusion of MSC was evaluated in female Wistar-Kyoto rats with myocardial infarction model using echocardiography, morphological study, morphometry, immunohistostaining, data from in situ hybridization, and by measurement of blood serum levels of nitric oxide, endothelin-1, vascular endothelial growth factor (VEGF), and fibroblast growth factor 2 (FGF2). Results The transplanted MSC were detected in all layers of the myocardium; MCS actively participate in the formation of blood vessels and connective tissue in the scar zone. There was no observable differentiation of male MSC into cardiomyocytes in female rats with MI. However, MSC transplantation leads to significant improvement in vascularization in the area of MI, elevation blood serum levels of nitric oxide, VEGF, and FGF2. No significant differences were identified morphologically between the two groups of animals after transplantation with unmodified MSC or commited MSC (5-azaC). Conclusion Intravenous transplantation of MSC without commitment in rats with MI improves the contractile function of the heart, the morphology of the myocardium, and should be recommended for further clinical investigation as an alternative approach to deal with heart diseases.

Advanced cardiac failure is a progressive intractable disease and is the main cause of mortality and morbidity worldwide. Since this pathology is represented by a definite decrease in cardiomyocyte number, supplementation of functional cardiomyocytes into the heart would hypothetically be an ideal therapeutic option. Recently, unlimited in vitro production of human functional cardiomyocytes was established by using induced pluripotent stem cell (iPSC) technology, which avoids the use of human embryos. A number of basic studies including ours have shown that transplantation of iPSCderived cardiomyocytes (iPSC-CMs) into the damaged heart leads to recovery of cardiac function, thereby establishing "proof-of-concept" of this iPSC-transplantation therapy. However, considering clinical application of this therapy, its feasibility, safety, and therapeutic efficacy need to be further investigated in the pre-clinical stage. This review summarizes up-to-date important topics related to safety and efficacy of iPSC-CMs transplantation therapy for cardiac disease and discusses the prospects for this treatment in clinical studies.

With the absence of a curative therapy, novel strategies to combat heart failure are urgently required. As an intriguing approach to restore the necrotic cardiac tissue, stem cell regenerative therapy has been broadly assessed. Recently, the placenta emerged as a unique stem cell source that is abundant and nonimmunogenic and shares many properties with adult and embryonic stem cells. Numerous stem cell populations can be isolated and identified within the placental layers. In this chapter, we have summarized the cardiomyogenic potential of placenta-derived stem cells addressed in vitro and in animal model studies. The exceptional properties of these cells, such as the expression of cardiac-specific markers and transcriptional factors, along with their lack of ethical conflicts and young age have shed the light on the placenta-derived stem cells as an appealing source that could mitigate ventricular remodeling and promote cardiac healing.

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

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 (

Cell transplantation via direct intramuscular injection is a promising therapy for patients with ischemic diseases. However, following injections, retention of transplanted cells in engrafted areas remains problematic, and can be deleterious to cell-transplantation therapy. In this Progress Report, a thermoresponsive hydrogel system composed of aqueous methylcellulose (MC) blended with phosphate-buffered saline is constructed to grow cell sheet fragments and cell bodies for the treatment of ischemic diseases. The as-prepared MC hydrogel system undergoes a sol-gel reversible transition upon heating or cooling at ≈32 °C. Via this unique property, the grown cell sheet fragments (cell bodies) can be harvested without using proteolytic enzymes; consequently, their inherent extracellular matrices (ECMs) and integrative adhesive agents remain well preserved. In animal studies using rats and pigs with experimentally created myocardial infarction, the injected cell sheet fragments (cell bodies) become entrapped in the interstices of muscular tissues and adhere to engraftment sites, while a minimal number of cells exist in the group receiving dissociated cells. Moreover, transplantation of cell sheet fragments (cell bodies) significantly increases vascular density, thereby improving the function of an infarcted heart. These experimental results demonstrate that cell sheet fragments (cell bodies) function as a cell-delivery construct by providing a favorable ECM environment to retain transplanted cells locally and consequently, improving the efficacy of therapeutic cell transplantation.

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 hours; however, an inflammatory response to the magnet was noted after 48 hours. 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.

Based on a porcine model with surgically created myocardial infarction (MI) as a pre-clinical scheme, this study investigates the clinical translation of cell sheet fragments of autologous mesenchymal stem cells (MSCs) for cellular cardiomyoplasty. MSC sheet fragments retaining endogenous extracellular matrices are fabricated using a thermo-responsive methylcellulose hydrogel system. Echocardiographic observations indicate that transplantation of MSC sheet fragments in infarcted hearts can markedly attenuate the adverse ventricular dilation and preserve the cardiac function post MI, which is in contrast to the controlled groups receiving saline or dissociated MSCs. Additionally, histological analyses suggest that administering MSC sheet fragments significantly prevents the scar expansion and left ventricle remodeling after MI. Immunohistochemistry results demonstrate that the engrafted MSCs can differentiate into endothelial cells and smooth muscle cells, implying that angiogenesis and the subsequent regional perfusion improvement is a promising mechanism for ameliorating post-infarcted cardiac function. However, according to the data recorded by an implantable loop recorder, the transplanted MSCs may provoke arrhythmia. Nevertheless, the proposed approach may potentially lead to the eventual translation of MSC-based therapy into practical and effective clinical treatments.

In coronary heart disease, the use of stem cells for regeneration purposes has been broadly studied. Whereas bone marrow mesenchymal stem cells remain the most extensively investigated, other cell sources have been reported. Here we discuss and compare the characteristics of placenta-derived mesenchymal stem cells as a novel alternative cell source for cellular cardiomyoplasty. These cells are isolated from the human term placenta, which is normally discarded post partum. With their lack of ethical conflicts and young age, the readily available placenta-derived mesenchymal stem cells could be more suitable for myocardial regenerative therapy.

Heart failure is the end-stage of many cardiovascular diseases—such as acute myocardial infarction—and remains one of the most appealing challenges for regenerative medicine because of its high incidence and prevalence. Over the last 20 years, cardiomyoplasty , based on the isolated administration of cells with regenerative capacity, has been the focal point of most studies aimed at regenerating the heart. Although this therapy has proved feasible in the clinical setting, the degree of infarcted myocardium regenerated and of improved cardiac function are at best modest. Hence, tissue engineering has emerged as a novel technology using cells with regenerative capacity, biological and/or synthetic materials, growth, proangiogenic and differentiation factors, and online registry systems, to induce the regeneration of whole organs or locally damaged tissue. The next step, seen recently in pioneering animal studies, is de novo generation of bioartificial hearts by decellularization and preservation of supporting structures for their subsequent repopulation with new contractile, vascular muscle tissue. Ultimately, this new approach would entail transplantation of the “rebuilt” heart, reestablishing cardiac function in the recipient.

Although static cardiomyoplasty prevents the left ventricle (LV) from dilatation, it may interfere with diastolic relaxation, or cause restriction. We developed a synthetic net with dual elasticity and tested its effect late after myocardial infarction in the rat. LV pressure-volume relationships (PVR) were successively analyzed before, after intravenous volume load, and 10 minutes after occlusion of the left anterior descending artery. Rats were then randomized into groups receiving synthetic net wrapping around the heart (NET+, n = 8) and only partially behind LV (NET-, n = 9), and they underwent the same PVR studies 6 weeks later. End-diastolic and end-systolic PVR were defined, and LV size and function were compared under standardized loading conditions. Although there was no difference in Day 0, increase in LV end-diastolic and end-systolic volumes were significantly attenuated in NET+ rats 6 weeks later when there was a significant correlation between LV volumes by PVR estimation and actual measurements, with significant differences in both measures between the groups: NET+ < NET-. The presence or absence of net did not show restrictive hemodynamics under acute volume load. Static cardiomyoplasty using a synthetic elastic net significantly attenuated LV dilatation and dysfunction without restriction late after myocardial infarction in the rat.

Heart failure is a life-threatening disorder worldwide and many papers reported about myocardial regeneration through surgical method induced by LVAD, cellular cardiomyoplasty (cell injection), tissue cardiomyoplasty (bioengineered cardiac graft implantation), in situ engineering (scaffold implantation), and LV restrictive devices. Some of these innovated technologies have been introduced to clinical settings. Especially, cell sheet technology has been developed and has already been introduced to clinical situation. As the first step in development of cell sheet, neonatal cardiomyocyte sheets were established and these sheets showed electrical and histological homogeneous heart-like tissue with contractile ability in vitro and worked as functional heart muscle which has electrical communication with recipient myocardium in small animal heart failure model. Next, as a preclinical study, noncontractile myoblast sheets have been established and these sheets have proved to secrete multiple cytokines such as HGF or VEGF in vitro study. Moreover, in vivo studies using large and small animal heart failure model have been done and myoblast sheets could improve diastolic and systolic performance by cytokine paracrine effect such as angiogenesis, antifibrosis, and stem cell migration. Recently evidenced by these preclinical results, clinical trials using autologous myoblast sheets have been started in ICM and DCM patients and some patients showed LV reverse remodelling, improved symptoms, and exercise tolerance. Recent works demonstrated that iPS cell-derived cardiomyocyte sheet were developed and showed electrical and microstructural homogeneity of heart tissue in vitro, leading to the establishment of proof of concept in small and large animal heart failure model.

Heart failure is a life threatening disorder in worldwide and many papers reported about myocardial regeneration through surgical method induced by LVAD, cellular cardiomyoplasty (cell injection), tissue cardiomyoplasty (bioengineered cardiac graft implantation), in situ engineering (scaffold implantation), and LV restrictive devices. Some of these innovated technologies have been introduced to clinical settings. This review article provides summary about recent basical and clinical advances about myocardial regeneration induced by bioengineered cardiac tissue.

This review explores the history, methods and evidence surrounding the various surgical therapeutic options which are available for patients with end-stage heart failure.

Progressive cardiac remodeling, including the myopathic process in the adjacent zone following myocardial infarction (MI), contributes greatly to the development of cardiac failure. Cardiomyoplasty using bone marrow-derived mesenchymal stem cells (MSCs) has been demonstrated to protect cardiomyocytes and/or repair damaged myocardium, leading to improved cardiac performance, but the therapeutic effects on cardiac remodeling are still under investigation. Here, we tested the hypothesis that MSCs could improve the pathological remodeling of the adjacent myocardium abutting the infarct. Allogeneic ovine MSCs were transplanted into the adjacent zone by intracardiac injection 4 hours after infarction. Results showed that remodeling and contractile strain alteration were reduced in the adjacent zone of the MSC-treated group. Cardiomyocyte hypertrophy was significantly attenuated with the normalization of the hypertrophy-related signaling proteins phosphatidylinositol 3-kinase α (PI3Kα), PI3Kγ, extracellular signal-regulated kinase (ERK), and phosphorylated ERK (p-ERK) in the adjacent zone of the MSC-treated group versus the MI-alone group. Moreover, the imbalance of the calcium-handling proteins sarcoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA2a), phospholamban (PLB), and sodium/calcium exchanger type 1 (NCX-1) induced by MI was prevented by MSC transplantation, and more strikingly, the activity of SERCA2a and uptake of calcium were improved. In addition, the upregulation of the proapoptotic protein Bcl-xL/Bcl-2-associated death promoter (BAD) was normalized, as was phospho-Akt expression; there was less fibrosis, as revealed by staining for collagen; and the apoptosis of cardiomyocytes was significantly inhibited in the adjacent zone by MSC transplantation. Collectively, these data demonstrate that MSC implantation improved the remodeling in the region adjacent to the infarct after cardiac infarction in the ovine infarction model.

Tissue-engineered scaffolds may improve experimental outcomes in cardiac cell therapy by targeted delivery of stem cells and mechanically support an infarcted left ventricular (LV) wall. We transplanted cardiomyocyte-like cells (5×105) with scaffolding via epicardial patching (cell patch, n=17) or a low-dose intramyocardial hydrogel (LD hydrogel, n=18), a high-dose (5×106) intramyocardial hydrogel (HD hydrogel, n=18) or transplanting a serum-free medium control (control, n=13), a blank patch (n=14), and a blank gel (n=16) for targeted cardiomyoplasty in a myocardial infarcted rat model. LV real-time hemodynamics were assessed using a 1.9-F pressure–volume catheter 7 weeks after stem cell transplantation. All mode of scaffold transplantation protected diastolic function by preserving LV wall integrity that resulted in a lower end diastolic pressure–volume relationship (EDPVR) as compared to a control medium-injected group. Moreover, epicardial patching, but not hydrogel injection, reduced ventricular wall stress with a significantly better LV end diastolic pressure (EDP: 5.3±2.4 mmHg vs. 9.6±6.9 mmHg, p

Cellular cardiomyoplasty employs stem cell therapy to regenerate myocardium. Characterized by their potential for proliferation, differentiation and capacity for self-renewal, stem cells are ideally suited for use in regenerative medicine. Supplementing traditional therapeutic modalities aimed at the palliation of congestive heart failure, cellular cardiomyoplasty is an innovative approach aimed at producing functional, viable myocardium following an acute infarction. The primary focus is to prevent the onset of congestive heart failure; however, potential applications aimed at reversing ischemic heart disease are concurrently in development. After decades of research, cellular cardiomyoplasty has moved beyond traditional in vitro and animal models; it is currently being implemented in clinical trials. Despite this monumental advance, certain limitations remain inherent in this process, preventing stem cell therapy from reaching its full potential. On a cellular level, stem cell retention and viability postimplantation continues to be problematic. Solutions under investigation include pioneering advances in cell delivery, in vitro pretreatment, and tissue engineering. Moreover, questions surrounding optimal cell type and cellular mechanisms concerning cellular cardiomyoplasty remain unanswered. Clarification of these issues is essential to ensure continued progression of this new technology. Stem cell therapy has been highly successful within the in vitro and in vivo environment. However, as clinical trials abound, cellular cardiomyoplasty must transition from an experimental concept to an effective therapeutic treatment. This process is hindered by discordance between scientific accrue and practical applicability. This review will provide a comprehensive summary of current innovations on cellular cardiomyoplasty, and future prospects. There will be a particular emphasis on the clinical aspects of stem cell therapy in an attempt to bridge the gap between science and medicine. Overcoming this barrier will render cellular cardiomyoplasty accessible to patients on a global basis.

Cellular cardiomyoplasty has been limited by poor graft retention after cell transplantation. To ensure good retention of the engrafted cells, a microfluidic device was used to fabricate spherical porous beads of poly(D,L-lactic-co-glycolic acid) as a platform for cell delivery. The beads thus obtained had a relatively uniform size, a highly porous structure, and a favorably interconnected interior architecture, to facilitate the transportation of oxygen and nutrients. These porous beads were loaded with human amniotic fluid stem cells (hAFSCs) to generate cellularized microscaffolds. Live/dead assay demonstrated that most of the cells in the porous constructs were viable. The hAFSCs that were grown in beads formed a complex three-dimensional organization with well-preserved extracellular matrices (ECM) according to their porous structure. Retention of the administered beads was clearly identified at the site of engraftment following an experimentally induced myocardial infarction in a rat model. The results of echocardiography, magnetic resonance imaging, and histological analyses suggest that the transplantation of hAFSC beads into an infarcted heart could effectively maintain its gross morphology, prevent successive ventricular expansion, and thereby improve the post-infarcted cardiac function. Immunofluorescent staining revealed that the microenvironment that was provided by the infarcted myocardium might offer cues for the induction of the engrafted hAFSCs into angiogenic and cardiomyogenic lineages. Our results demonstrate that the cellularized beads with endogenously secreted ECM were of sufficient physical size to be entrapped in the interstitial tissues following transplantation, thereby benefiting the infarcted heart.

Background: Human mesenchymal stem cells (hMSCs) show potential for therapeutic cellular cardiomyo- plasty. However, a range of delivery methods, including direct intramyocardial injection, have resulted in poor engraftment in vivo. We used the in vivo rat heart model to study hMSC engraftment and retention in a normal beating heart. Materials and Methods: HMSCs transfected with green fluorescent protein were injected into the left ventricle (LV) of immunocompetent rats. Hearts were cryopreserved 30 minutes (Group A), 24 hours (Group B), and 5 days (Group C) post hMSC delivery. HMSC retention was estimated using confocal fluorescence microscopy and immunohistochemistry. Measured values were compared to projected GFP-positive cellular volumes. Immunohistochemical analyses probed for the presence of human cells with human prolyl 4-hydroxylase beta (p4hβ) and an immune response with murine monocyte/macrophage antigen (CD68). Results: HMSC retention decreased significantly from 30 minutes to 5 days (p

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

In adult organisms, when stimulation of skeletal muscle is stopped, all changes revert to control after 10–14 days. This is the reason that training of the skeletal muscle before cardiomyoplasty is not done. We hypothesized that the muscle of a growing organism would not revert during a delay. Four lambs received 8 weeks of electrical stimulation of the left latissimus dorsi muscle (LDM) with the right LDM as control. Contractility force and positive and negative dF/dt were measured after 8 weeks conditioning, 2 weeks delay, and control. Conditioned muscle during a 30-minute fatigue test had decreased contractile force on an average of 7±2%; control muscle had decreased contractile force on an average of 39±4%; and after 2 weeks delay, there was a decrease in the contractile force of 12±2%. A stronger fatigue test was performed after 10 minutes of rest. Conditioned muscle lost an average of 15±5% of their contractile force, 16±2% positive dF/dt, and 14±2% negative dF/dt. Control muscle lost 40±3%, 39±4%, and 42±5%, respectively. After 2 weeks delay, previously conditioned muscle showed the following decreases: contractile force 21±3%, positive dF/dt 19±3%, and negative dF/dt 16±3%. Skeletal muscle biopsies were also taken and levels of lactate dehydrogenase (LDH) fractions were measured. LDH fractions one and two (LDH-1 + 2) after 8 weeks conditioning consisted of 6.7±1.9% (p

Objective: Previous regenerative studies have demonstrated massive cell losses after intramyocardial cellular delivery. Therefore, efforts at reducing mechanical losses may prove more successful in optimising cellular therapy. In this study, we hypothesized that escalating mesenchymal stem cells (MSCs) dose will not produce corresponding improvement in cardiac function due to washout of the small cells in microcirculation. Using microspheres similar in size to MSCs, that are encapsulated in alginate-poly-L-lysine-alginate (APA), we tested the hypothesis that size is an important factor in early losses. Methods:In experiment I, five groups of rats (n = 9 each) underwent coronary ligation; group I had no treatment; the other groups received escalating 0.5 � 10 6 , 1.5 � 10 6 ,3 � 10 6 and 5 � 10 6 of MSCs each. Echocardiogram was performed at baseline, 2 days and 7 weeks after surgery. In experiment II, cell-sized microspheres (10 mm) were encapsulated in APA microcapsules. In group I (n = 16), rats received bare microspheres, group II (n = 16) microspheres within 200 mm microcapsules and in group III (n = 16), microspheres within 400 mm microcapsules. After 20 min, hearts were quantified for the amount retained. Results: Myocardial function did not improve further with escalatingcell dosesbeyondan initialresponse at1.5 � 10 6 cells.Encapsulatedmicrospheresin200 mm and 400 mm microcapsules demonstrated a fourfold increase in retention rate compared with 10 mm microspheres. Conclusion: We concluded that suboptimal functional improvement in this animal model starts at 1.5 � 10 6 cells and does not respond to escalating cell doses. Improving mechanical retention is possible by increasing the size of the injectate. Microencapsulation could be used to encapsulate donor cells and facilitate functional improvement in cellular heart failure therapy. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Chronic heart failure is one of the major health care issues in terms of increasing number of patients, rate of hospitalizations and costs. Heart transplantation is the best established therapy for patients with severe heart failure. However, the number of donors limits the activity to 5000 heart transplants performed annually worldwide. This limitation has generated alternative treatments. The increase of the interest in the reversibility of the heart failure and the application of new biological alternatives has generated therapeutic strategies designed to integrate biology and medical technologies in order to act to the biomechanical, the molecular and the neurohormonal mechanisms of heart failure. These treatments include cellular cardiomyoplasty, tissue engineering, surgical left ventricular restoration as well as passive and active mechanical ventricular assistance as destination therapy, bridge to recovery or bridge to transplantation. The integrated development of these approaches could offer hopeful treatments, although there is still much to be learned regarding the optimal use of these strategies.

Several recent basic research studies have described surgical methods for cardiac repair using tissue cardiomyoplasty. This review summarizes recent advances in cardiac repair using bioengineered tissue from the viewpoint of the cardiac surgeon. We conclude that the results of many basic and preclinical studies indicate that bioengineered tissue can be adapted to conventional surgical techniques. However, no clinical studies have yet proved bioengineered tissue is effective as a treatment for human heart failure. Today's cardiac surgeons can look forward to the advent of new techniques to benefit patients who respond poorly to existing treatment for heart failure.

GIL, J. & OLIVARES, R. A biceps muscle Latissimus dorsi in a dog. Int. J. Morphol., 32(4):1464-1466, 2014.SUMMARY: This article reports the finding of a twin unreported muscle begin. In one dog, both, left and right muscle latissimusdorsi were biceps. The thin second head of m. latissimus dorsi that we founded, could be an intermediate step of comparative anatomychanges from reptilian to mammal. Man breast surgery and cardiomyoplasty, use dog latissimus dorsi as experimental, to know thisinformation can be useful to these situations.KEY WORDS: Muscle; M. Latissimus dorsi; Dog; M. Biceps; Arm.

Cellular cardiomyoplasty is under extensive investigation as a potential therapeutic strategy after myocardial infarction, in congestive heart failure and chronic ischemic heart disease. Various cell sources and techniques for transplantation have been studied in animal models of cardiac disease. The initial goal of replacing myocardial scar tissue by vital myocardial cells, integrated into the host, simultaneously beating and contributing to systolic force, has not yet been accomplished. However, most experimental models provided evidence for enhanced vascularization after cell transplantation. In some investigations, neovascularization was also shown to be accompanied by increased myocardial perfusion. Mechanisms by which vascularization occurs have not been fully elucidated: either the transplanted cells provide an angiogenic stimulus, involving various paracrine or hormone-like factors, which induces the formation of a new vasculature or, depending on the source of transplanted cells, the cells incorporate into the vascular network after proliferation and differentiation. This review summarizes research that specifically studied the occurrence, magnitude and mechanisms of enhanced myocardial blood supply after cellular cardiomyoplasty

Sudden death represents a common event in the natural history of patients affected by chronic heart failure. Such an outcome also has been shown to characterize the follow-up of the cardiomyoplasty procedure. We report two cases of patients who had cardiomyoplasty and experienced witnessed episodes of ventricular arrhythmia at variable times after surgery (2 years and 2 months, respectively). In the first case, an implantable cardioverter defibrillator (ICD) was implanted subsequent to the arrhythmic episode, whereas the second patient had a combined cardiomyoplasty and ICD implantation procedure. In particular, this patient underwent a modified wrapping technique, herein described, because of a large left ventricular dilatation. In both cases, ventricular defibrillation did not affect the correct functioning of the implanted cardiomyostimulator. Our article confirms that ventricular arrhythmia is common in cardiomyoplasty patients. The combined use of a skeletal muscle stimulator and implantable defibrillator may therefore be effective in preventing arrhythmia-related sudden death without any concurrent effect on the correct functioning of the wrapped muscle/heart circuit, with likely benefit on long-term cardiomyoplasty patient survival.

Muscle necrosis has been frequently observed in cardiomyoplasty patients and in experimental animal studies. The purpose of this study was to determine if heat shock could provide protection to skeletal muscle as has been shown in cardiac muscle. A 15-minute heat shock at 42 degrees C resulted in an immediate increase in HSP72 mRNA and was followed within 3 hours by a two-fold increase in HSP72. Surgical dissection of the latissimus dorsi muscle (LDM) followed by an ischemic period resulted in a two-fold increase in HSP72 in control LDM, whereas the already high levels in the heat-shocked LDM increased only slightly with surgery and ischemia. Citrate synthase activity and tissue histology indicated that heat shock did not protect the LDM from the imposed surgical trauma and ischemia insults used in this study.

Heart diseases, including myocardial infarction (MI) and congestive heart failure (CHF), have high mortality rates. Both MI and CHF are characterized by cardiac muscle damage caused by massive cardiomyocyte death and reduced cardiac function. Cellular therapy aimed at using cells to improve cardiac function and/or regenerate new myocardium, has been extensively investigated for cardiac repair. Two strategies have been currently taken for cellular transplantation, including in situ cellular cardiomyoplasty and cardiac tissue engineering. The in situ cellular cardiomyoplasty strategy delivers cells directly into the infarcted myocardium. A variety of cell types has been shown to be beneficial in cardiac repair. However, this strategy is limited in terms of cell retention, survival of the engrafted cells, cell differentiation, and integration of transplanted cells with host tissue. Cardiac tissue engineering is an alternate strategy to in situ cellular cardiomyoplasty, which is designed to repair infarcted myocardium using cells, biomaterials and regulative factors (for example growth factors). There are currently various approaches for cardiac tissue engineering, such as, in situ delivering cells with injectable biomaterials into the infarcted myocardium, in vitro engineering of contractile tissue constructs followed by in vivo implantation, in vitro engineering of stem cell loaded tissue constructs for in vivo myocardium regeneration, and cell sheet tissue engineering. This review provides a comprehensive progress of in situ cellular cardiomyoplasty and cardiac tissue engineering for cardiac repair.

The notion of cell transplantation into the heart as a means of reversing ischemic injury is now nearly a decade old. The first clinical application of bone marrow mononuclear cells (BMCs) for myocardial infarction was in 2001,1 presumably motivated at least in part by the premise that BMCs injected into the heart can directly regenerate new, functional myocardium.2 Although subsequent investigators questioned the ability of BMCs to transdifferentiate into cardiomyocytes3,4 (but in all fairness, others did support the idea5,6), the horse was out of the barn, and the treatments continued apace. Fortunately, injection of autologous BMCs as adjunctive treatment for convalescent myocardial infarction has proven to be remarkably safe.7–9 Although the overall efficacy is modest, certain subgroups (particularly those with large functional deficits at baseline) do experience clinically meaningful increments in ejection fraction.10,11 A related consideration arises in the choice of cell type to transplant. BMCs, although easy to harvest, are almost certainly not the best candidate cells for cardiomyoplasty, because they are not specialized to regrow normal healthy heart muscle. An attractive alternative arose with the recognition that the adult heart contains its own reservoir of progenitor cells,12–15 some of which express the stem cell antigen c-kit.12,14 Such cardiac progenitor cells (CPCs) presumably function physiologically to mediate a low basal turnover rate of cardiomyocytes in the adult heart16 but may be expanded and exploited iatrogenically for more focused (and, mechanistically, more rational) benefit than may be possible with BMCs. When injected into the injured heart, CPCs increase tissue viability12,14,17–20 and improve ventricular function.12,14,17,20 Articles see p 1992 and p 2001 Ironically, we are now less certain about the mechanism of cell therapy than we thought we were a decade ago, when it seemed that direct regeneration of tissue …

The concept of bionics was developed 50 years ago and represented the development of engineering and technology based on natural biological systems. Traditional applications of bionics in healthcare include artificial bionic organs that apply engineering principles to replace or augment physiological functions by integrating electronic, mechanical or electromechanical components to inherent body tissues/organs (we term this as ‘exobionics’). Recently, there has been a new wave of bio-inspired treatments that act through the reorganization of the existing biological organs in an individual to enhance physiology. Here, the technology does not replace biological tissue, but rather applies engineering principles to replace or augment physiological functions by the rearrangement and manipulation of inherent tissue/organs; we term this autobionics. Examples include: dynamic cardiomyoplasty (artificial heart pump using skeletal muscle), the Ross procedure (pulmonary autograft), dynamic graciloplasty (artificial sphincter) and metabolic gastric bypass (rearranging the gastrointestinal tract to modify gut- and pancreatic-hormone release). Autobionic therapies can be classified into dynamic, static and metabolic procedures. This results in tissue redesignation (one tissue used in place of another), tissue replacement and systems reorganization (rearranging inherent organ/tissue anatomy). In some cases autobionic procedures can enhance physiological function beyond normality and represents a new era in bio-inspired versatility.

The French multicenter experience (6 centers) of dynamic cardiomyoplasty was analyzed for long-term survival and functional outcome, the most important endpoints in congestive heart failure therapy. Cardiomyoplasty was performed in 212 patients with symptoms of chronic heart failure despite maximal pharmacological therapy. The etiology was ischemic (48%), idiopathic (45%) or other (7%). Cardiomyoplasty was performed using the latissimus dorsi muscle which was electrostimulated after surgery. During follow-up, 88% of patients improved clinically. Hospital death occurred in 29 (14%) patients and was related to the severity of preoperative heart failure symptoms. Late mortality occurred in 99 patients due to heart failure (44%), sudden death (37%), or noncardiac causes (18%). Combined dynamic cardiomyoplasty and implantation of a cardiac rhythm management system was safely achieved in 22 patients, and 26 underwent heart transplantation for recurrent heart failure. Long-term functional improvements were observed in most patients, and the best outcome was achieved in those with isolated right ventricular failure. Dynamic cardiomyoplasty can be considered as a destination therapy or a mid- to long-term biological bridge to heart transplantation.

Background Until now, cell therapy has constituted a passive therapeutic approach; the only effects seem to be related to the reduction of the myocardial fibrosis and the limitation of the adverse ventricular remodeling. Cardiac resynchronization therapy is indicated in patients with heart failure to correct conduction disorders associated with chronic systolic and diastolic dysfunction. The association of electrostimulation with cellular cardiomyoplasty could be a way to transform passive cell therapy into "dynamic cellular support." Electrostimulation of ventricles following skeletal myoblast implantation should induce the contraction of the transplanted cells and a higher expression of slow myosin, which is better adapted for chronic ventricular assistance. The purpose of this study is to evaluate myogenic cell transplantation in an ischemic heart model associated with cardiac resynchronization therapy. Methods Twenty two sheep were included. All animals underwent myocardial infarction by ligation of 2 coronary artery branches (distal left anterior descending artery and D2). After 4 weeks, autologous cultured myoblasts were injected in the infarcted areas with or without pacemaker implantation. Atrial synchronized biventricular pacing was performed using epicardial electrodes. Echocardiography was performed at 4 weeks (baseline) and 12 weeks after infarction. Results Echocardiography showed a significant improvement in ejection fraction and limitation of left ventricular dilatation in cell therapy with cardiac resynchronization therapy as compared with the other groups. Viable cells were identified in the infarcted areas. Differentiation of myoblasts into myotubes and enhanced expression of slow myosin heavy chain was observed in the electrostimulated group. Transplantation of cells with cardiac resynchronization therapy caused an increase in diastolic wall thickening in the infarcted zone relative to cells-only group and cardiac resynchronization therapy–only group. Conclusions Biventricular pacing seems to induce synchronous contraction of transplanted myoblasts and the host myocardium, thus improving ventricular function. Electrostimulation was related with enhanced expression of slow myosin and the organization of myoblasts in myotubes, which are better adapted at performing cardiac work. Patients with heart failure presenting myocardial infarct scars and indication for cardiac resynchronization therapy might benefit from simultaneous cardiac pacing and cell therapy.

Heart failure accounts for more deaths in the United States than any other detrimental human pathology. Recently, repairing the heart after seemingly irreversible injury leading to heart failure appears to have come within reach. Cellular cardiomyoplasty, transplanting viable cell alternatives into the diseased myocardium, has emerged as a promising possible solution. Translating this approach from the laboratory to the clinic, however, has been met with several challenges, leaving many questions unanswered. This review assesses the state of investigation of several progenitor cell sources, including induced pluripotent stem cells, embryonic stem cells, bone marrow stem cells, adipose-derived adult stem cells, amniotic fluid stem cells, skeletal muscle progenitors, induced pluripotent stem cells and cardiac progenitors. Several current roadblocks to maximum success are discussed. These include understanding the need for cardiomyocyte differentiation, appreciating the role of paracrine factors, and addressing the low engraftment rates using current techniques. Tissue engineering strategies to address these obstacles and to help maximize cellular cardiomyoplasty success are reviewed.

Cell transplantation via direct intramyocardial injection is a promising therapy for patients with myocardial infarction; however, retention of the transplanted cells at the injection sites remains a central issue following injection of dissociated cells. Using a thermoresponsive hydrogel system with a multiwell structure, we successfully developed an efficient technique to generate spherically symmetric bodies of mesenchymal stromal cells (MSCs) inherent with endogenous extracellular matrices (ECMs) for direct intramyocardial injection. After injection through a needle and upon transferring to another growth surface, the time required to attach, migrate, and proliferate was significantly shorter for the MSC bodies than the dissociated MSCs. Employing a syngeneic rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were four treatment groups (n = 10): sham, phosphate-buffered saline, dissociated MSCs, and MSC bodies. The results obtained in the echocardiography and catheterization measurements demonstrated that the MSC body group had a superior heart function to the dissociated MSC group. Histologically, it was found that MSC bodies could provide an adequate physical size to entrap into the interstices of muscular tissues and offer a favorable ECM environment to retain the transplanted cells intramuscularly. Additionally, transplantation of MSC bodies stimulated a significant increase in vascular density, thus improving the cardiac function. These results indicated that the spherically symmetric bodies of MSCs developed in the study may serve as a cell-delivery vehicle and improve the efficacy of therapeutic cell transplantation.

Cardiac assistance from skeletal muscle offers an attractive surgical solution to the problem of end-stage heart failure, yet it is widely regarded as a failed approach. I argue here that this is an outdated assessment. Systematic progress has been made over the last 25 years in understanding the relevant basic science. In the light of these advances we should be reconsidering the place of skeletal muscle assist in the surgical armamentarium.

Evaluate the effects of pressure and duration of intracoronary (IC) infusion of mesenchymal stem cells (MSCs) on delivery efficiency and safety after myocardial infarction (MI).Standard IC delivery of MSCs can lead to intravascular plugging and reduced coronary blood flow. The optimal delivery pressure and duration is unknown.Immediately after MI pigs were randomized to 1 of 3 delivery protocols of 5 x 10(7) iron-fluorescent microspheres labeled MSCs, control received 2 ml infusions at 1 ml/min (five times), very high flow rate (VHFR) a single 10 ml infusion at 60 ml/min and the high flow rate (HFR) group a single 10 ml infusion at 20 ml/min. TIMI grade flow was assessed throughout the procedure and at sacrifice (day 14). MSCs distribution was analyzed in isolated hearts by 4.7T MRI. Delivery efficiency was quantified via fluorescent microsphere recovery using a magnetic separation technique and by light microscopy.TIMI grade flow did not change following MI (all groups TIMI 3). However, following MSCs delivery only 18% (2/11) of control animals had TIMI 3 blood flow vs. 56% (5/9) in VHFR and 67% (4/6) in HFR (P = 0.03). As a consequence, 63% of control animals died within 24 hr, 33% in VHFR and none in HFR (P = 0.02). MSCs delivery in the infarct tissue did not differ between the groups (P = 0.06).A single MSCs infusion at 20 ml/min resulted in improved coronary blood flow and decreased mortality, without sacrificing delivery efficiency.

Summary The glandular stem cell cardiomyopexy should become a treatment option for end-stage heart failure. It combines an expected regenerative potential of transformed adult glandular stem cells into cardiomyocytes within the myocardium or onto the myocardium of the recipient and the potential of a hypercapillarized latissimus dorsi muscle (LDM) wrapped around the heart for stem cell nutrition and girdling.

The effectiveness of dynamic cardiomyoplasty (DCMP) remains controversial. We hypothesized that effectiveness of DCMP using the latissimus dorsi muscle graft (LDMG) depends on the wrapping method. We analyzed pressure-volume relations (PVR), the left ventricular stroke work (LVSW), and the left ventricular end diastolic volume (LVEDV) changes during nonstimulation and stimulation of the LDMG to evaluate the effect of a new wrapping method of DCMP on the LVSW and the LVEDV changes. The new wrapping technique was evaluated in an acute animal experimental model. In 12 mongrel dogs, we performed continuous measurement of the dimensional and pressure dates of the left ventricle (LV) after the DCMP. The measurement was performed 15 min after wrapping during 5 periods. The duration of one measurement period was 15 s. The animals were divided into 2 groups according to the wrapping method. The heart was wrapped with the LDMG using 2 different methods. For Method 1, Carpentier's method, the heart was wrapped primarily with the distal part of the LDMG, the lateral segment. The vasculoneural pedicle of the latissimus dorsi muscle (LDM) was preserved. For Method 2, the LDM was separated, and the vasculoneural pedicle was cut. The medical sternotomy was performed. The thoracodorsal artery of LDMG was anastomosed to the right internal mammary artery, and the thoracodorsal vein was anastomosed to the right atrial appendage. The heart was wrapped primarily with the proximal part of the "free LDMG," the transverse segment. Based on the PVR loops, the changes of the LVSW and the LVEDV in both experimental groups were analyzed. The paired t-test was used for statistical analysis. Using Method 1, the LVSW and the LVEDV showed no significant changes during stimulation (stim) of the LDMG, compared with nonstimulation (nonstim) (LVSW: nonstim, 970 +/- 168 erg x 10(3); stim, 1,181 +/- 203 erg x 10(3); p = 0.126 and LVEDV: nonstim, 36.6 +/- 6.7 ml; stim, 37.2 +/- 6.8 ml; p = 0.36). Using Method 2, the LVSW was increased, and the LVEDV was decreased during stimulation of the free LDMG, compared with nonstimulation (LVSW: nonstim, 694 +/- 117 erg x 10(3); stim, 846 +/- 104 erg x 10(3); p < 0.001 and LVEDV: nonstim, 47.7 +/- 2.8 ml; stim, 46.8 +/- 2.7 ml; p < 0.001). The stimulated free LDMG wrapping of the heart seems to be a more effective wrapping method for DCMP, and it results in an increase of the LVSW and a decrease of the LVEDV, compared with the original Carpentier's method.