Dynamic cardiomyoplasty in patients with end-stage heart failure: anaesthetic considerations.
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Dynamic cardiomyoplasty is used increasingly for patients with chronic heart failure, with approximately 500 cases having been performed. The latissimus dorsi muscle is prepared maintaining its vascular supply and the muscle flap is wrapped around the heart and connected to a cardiomyostimulator. The muscle is later stimulated synchronously with ventricular systole to augment the heart. Our experience of 22 patients with chronic heart failure (NYHA III-IV) undergoing dynamic cardiomyoplasty is described from the anaesthetist's point of view. Two patients are reported as case reports. The challenge is to manage patients with severely impaired left ventricular function, who do not obtain immediate benefit from the operation. Our experience supports the importance of early use of inotropic agents. (+info)
Cellular cardiomyoplasty improves survival after myocardial injury.
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BACKGROUND: Cellular cardiomyoplasty is discussed as an alternative therapeutic approach to heart failure. To date, however, the functional characteristics of the transplanted cells, their contribution to heart function, and most importantly, the potential therapeutic benefit of this treatment remain unclear. METHODS AND RESULTS: Murine ventricular cardiomyocytes (E12.5-E15.5) labeled with enhanced green fluorescent protein (EGFP) were transplanted into the cryoinjured left ventricular walls of 2-month-old male mice. Ultrastructural analysis of the cryoinfarction showed a complete loss of cardiomyocytes within 2 days and fibrotic healing within 7 days after injury. Two weeks after operation, EGFP-positive cardiomyocytes were engrafted throughout the wall of the lesioned myocardium. Morphological studies showed differentiation and formation of intercellular contacts. Furthermore, electrophysiological experiments on isolated EGFP-positive cardiomyocytes showed time-dependent differentiation with postnatal ventricular action potentials and intact beta-adrenergic modulation. These findings were corroborated by Western blotting, in which accelerated differentiation of the transplanted cells was detected on the basis of a switch in troponin I isoforms. When contractility was tested in muscle strips and heart function was assessed by use of echocardiography, a significant improvement of force generation and heart function was seen. These findings were supported by a clear improvement of survival of mice in the cardiomyoplasty group when a large group of animals was analyzed (n=153). CONCLUSIONS: Transplanted embryonic cardiomyocytes engraft and display accelerated differentiation and intact cellular excitability. The present study demonstrates, as a proof of principle, that cellular cardiomyoplasty improves heart function and increases survival on myocardial injury. (+info)
Myocardial regeneration therapy for heart failure: hepatocyte growth factor enhances the effect of cellular cardiomyoplasty.
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BACKGROUND: We hypothesized that transfection of the gene for human hepatocyte growth factor (hHGF) combined with cellular cardiomyoplasty might regenerate the impaired myocardium. METHODS AND RESULTS: We used a ligation model of proximal left anterior descending coronary artery (LAD) of Lewis rats. Two weeks after LAD ligation, 3 different treatments were conducted: (1) neonatal rat cardiomyocytes group (10(6) cells, T group, n=11), (2) HVJ-liposomes bearing the hHGF gene group (H group, n=10), and (3) combined (T-H group, n=10). The injection site was the scar area of myocardial infarction. For control, culture medium was injected (C group, n=13). Echocardiography demonstrated that cardiac performance was significantly ameliorated in the T-H group 4 and 8 weeks after injection. Contrast echocardiography also showed a marked increase in myocardial perfusion in the T-H group but not in the other groups. In the T-H group, neovascularization and a marked reduction of fibrosis were observed histologically. In an immunohistochemical study, strong staining for beta(1)-integrin, alpha-, and beta-dystroglycan were found principally in the basement membrane of myocytes in the T-H group 8 weeks after transplantation, although there was weak immunoreactivity in the T group. CONCLUSIONS: hHGF gene transfection enhanced the cellular cardiomyoplasty possibly by stimulating angiogenesis, restoring the impaired ECM, and promoting the integration of the dissociated grafted myocytes. The combined effects might have lead to the improved cardiac performance. Thus, combined therapy may be a promising strategy for the treatment of heart failure caused by myocardial infarction. (+info)
Mechanical properties of the latissimus dorsi muscle after cyclic training.
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Cardiomyoplasty is a procedure developed to improve heart performance in patients suffering from congestive heart failure. The latissimus dorsi (LD) muscle is surgically wrapped around the failing ventricles and stimulated to contract in synchrony with the heart. The LD muscle is easily fatigued and as a result is unsuitable for cardiomyoplasty. For useful operation as a cardiac-assist device, the fatigue resistance of the LD muscle must be improved while retaining a high power output. The LD muscle of rabbits was subjected to a training regime in which cyclic work was performed. Training transformed the fiber-type composition from approximately equal proportions of fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibers to one composed of almost entirely of FOG with no FG, which increased fatigue resistance while retaining rapid contraction kinetics. Muscle mass and cross-sectional area increased but power output decreased, relative to control muscles. This training regime represents a significant improvement in terms of preserving muscle mass and power compared with other training regimes, while enhancing fatigue resistance, although some fiber damage occurred. The power output of the trained LD muscle was calculated to be sufficient to deliver a significant level of assistance to a failing heart during cardiomyoplasty. (+info)
Cellular cardiomyoplasty of cardiac fibroblasts by adenoviral delivery of MyoD ex vivo: an unlimited source of cells for myocardial repair.
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BACKGROUND: The muscle-specific MyoD family of transcription factors function as master genes that are able to prompt myogenesis in a variety of cells. The purpose of our study was to determine whether MyoD could induce primary cardiac fibroblasts, isolated from infarcted myocardium or pericardium, to undergo myogenic conversion in a clinically relevant approach. METHODS AND RESULTS: Primary rat fibroblasts from 7-day-old infarcted myocardium or normal pericardium were transfected by an E1/E3-deleted adenoviral vector carrying both a human MyoD cDNA driven by a CMV promoter and a green fluorescent protein (GFP) reporter gene driven by a second CMV promoter. Expression of MyoD caused myogenic differentiation of cultured fibroblasts, as defined by elongation and fusion into multinucleated myotubes, typical cross striation as identified by electron microscopy, and positive immunostaining for sarcomeric actin, fast myosin heavy chain (MHC), and actinin. The myogenic cells (1.5x10(6)) were transplanted into the infarcted myocardium 7 days after coronary artery occlusion. By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of myogenic cells that in a few hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins fast-MHC and sarcomeric actin. A few cells expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of untreated fibroblasts or culture medium. CONCLUSIONS: Our work shows that it is possible to exploit the unique capacity of MyoD to activate myogenesis in fibroblasts ex vivo and to create a vast source of autologous myogenic cells for transplantation. (+info)
Experience in heart transplantation after dynamic cardiomyoplasty.
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We report a case undergoing heart transplantation due to gradual progression of heart failure four years and one month after dynamic cardiomyoplasty. This case reports a 61-year-old man who received drug therapy after being diagnosed as having idiopathic dilated cardiomyopathy, but his heart failure progressed to New York Heart Association (NYHA) class III-IV, and heart transplantation was thought to be indicated. However, dynamic cardiomyoplasty was performed because this patient rejected heart transplantation. An implantable cardioverter/defibrillator (ICD) was implanted for postoperative ventricular arrhythmia. After that, his symptoms rapidly improved, but his heart failure gradually worsened two years after surgery and heart transplantation was performed four years and one month after dynamic cardiomyoplasty. Since transplantation he has had an uneventful postoperative course without rejection or complications. (+info)
Tissue engineering therapy for cardiovascular disease.
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The present treatments for the loss or failure of cardiovascular function include organ transplantation, surgical reconstruction, mechanical or synthetic devices, or the administration of metabolic products. Although routinely used, these treatments are not without constraints and complications. The emerging and interdisciplinary field of tissue engineering has evolved to provide solutions to tissue creation and repair. Tissue engineering applies the principles of engineering, material science, and biology toward the development of biological substitutes that restore, maintain, or improve tissue function. Progress has been made in engineering the various components of the cardiovascular system, including blood vessels, heart valves, and cardiac muscle. Many pivotal studies have been performed in recent years that may support the move toward the widespread application of tissue-engineered therapy for cardiovascular diseases. The studies discussed include endothelial cell seeding of vascular grafts, tissue-engineered vascular conduits, generation of heart valve leaflets, cardiomyoplasty, genetic manipulation, and in vitro conditions for optimizing tissue-engineered cardiovascular constructs. (+info)
Percutaneous transvenous cellular cardiomyoplasty. A novel nonsurgical approach for myocardial cell transplantation.
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OBJECTIVES: The study evaluated a nonsurgical means of intramyocardial cell introduction using the coronary venous system for direct myocardial access and cell delivery. BACKGROUND: Direct myocardial cell repopulation has been proposed as a potential method to treat heart failure. METHODS: We harvested bone marrow from Yorkshire swine (n = 6; 50 to 60 kg), selected culture-flask adherent cells, labeled them with the gene for green fluorescence protein, expanded them in culture, and resuspended them in a collagen hydrogel. Working through the coronary sinus, a specialized catheter system was easily delivered to the anterior interventricular coronary vein. The composite catheter system (TransAccess) incorporates a phased-array ultrasound tip for guidance and a sheathed, extendable nitinol needle for transvascular myocardial access. A microinfusion (IntraLume) catheter was advanced through the needle, deep into remote myocardium, and the autologous cell-hydrogel suspension was injected into normal heart. Animals were sacrificed at days 0 (n = 2), 14 (n = 1, + 1 control/collagen biogel only), and 28 (n = 2), and the hearts were excised and examined. RESULTS: We gained widespread intramyocardial access to the anterior, lateral, septal, apical, and inferior walls from the anterior interventicular coronary vein. No death, cardiac tamponade, ventricular arrhythmia, or other procedural complications occurred. Gross inspection demonstrated no evidence of myocardial perforation, and biogel/black tissue dye was well localized to sites corresponding to fluoroscopic landmarks for delivery. Histologic analysis demonstrated needle and microcatheter tracts and accurate cell-biogel delivery. CONCLUSIONS: Percutaneous intramyocardial access is safe and feasible by a transvenous approach through the coronary venous system. The swine offers an opportunity to refine approaches used for cellular cardiomyoplasty. (+info)