We review our experience from January 1987 to September 1992 with the surgical treatment of complex congenital malformations requiring an extracardiac homograft-valved conduit. There were 10 patients in the series; 7 pulmonary and 3 aortic homografts were implanted. Ages ranged from 1 month to 26 years (mean 7.9). There were 4 cases of hospital mortality, none related to the homograft itself. The major postoperative complication was low cardiac output syndrome. The 6 survivors have been followed between 3 months and 5 years and no dysfunction of the valved homograft, thromboembolism, or hemolysis have been recorded. All the survivors are symptom-free with a good quality of life. The use of homografts is advised in selected cases of right and left ventricular tract reconstruction for congenital heart disease; homografts are easy to handle and offer several technical advantages over prosthetic tissues.
Minimally invasive techniques for repair of extracardiac anomalies in congenital heart disease have evolved over the last 5 years and laid the foundation for the next phase: the repair of intracardiac defects. Fifteen patients (9 females and 6 males) with a median age of 9.8 years (range, 5.2 to 54 years) underwent closure of a secundum atrial septal defect through a small right anterior thoracotomy. The right external iliac artery was cannulated through a small groin incision and the atrial septal defect was repaired during hypothermic fibrillatory arrest for a mean period of 14 ± 5 minutes. The mean length of the thoracotomy was 4.9 ± 0.8 cm (range, 4.5 to 8.8 cm) while the mean length of the groin incision was 3.9 ± 0.5 cm (range, 2.9 to 5.3 cm). In the 3 youngest patients, the external iliac artery was cannulated with an 8F arterial cannula. Direct closure of the atrial septal defect was possible in all patients. The mean operative time was 109 ± 39 minutes. There was no perioperative or late mortality and no morbidity except for a tear in the right femoral artery of a 19-year-old girl. No residual atrial septal defect was observed in any of the patients. Although minimally invasive techniques for repair of intracardiac defects are not fully developed with regard to indications, the procedure described here provided secure closure of the defects with excellent cosmetic results.
Therapeutic angiogenesis using vascular endothelial growth factor can reduce tissue ischemia by simulating the natural process of angiogenesis. Vascular endothelial growth factor not only stimulates endothelial cells to proliferate and migrate, but also mobilizes endothelial progenitor cells and achieves vascular protection. Besides direct administration of angiogenic proteins, plasmids and viral vectors carrying angiogenic genes have been used. Animal experiments have shown promise with evidence of neovascularization and improved perfusion in the target myocardium. Initial phase I and II clinical trials results are encouraging and reflect the potential success of therapeutic angiogenesis as a clinical modality for the treatment of ischemic heart disease. This review discusses the role of vascular endothelial growth factor in therapeutic angiogenesis, along with the problems and considerations of this approach as a treatment strategy.
Skeletal myoblast (SkM) transplantation has been extensively investigated as a potential treatment modality in cardiovascular therapeutics, and the functional benefi ts of this procedure have been validated in animal models and clinical studies. 1 Preclinical studies have well demonstrated that SkM is a safe and effi cient cell type for cardiac repair. It improves systolic and diastolic function, increases myocardial wall thickness, and delimits the ventricular remodeling process. Skeletal myoblasts are as effective as neonatal cardiomyocytes
A potentially more effective means of surgical treatment for single vessel coronary artery disease has evolved with the development of a minimally invasive technique for surgical myocardial revascularization. We describe the case of a 43-year-old male with a history of proximal left anterior descending coronary artery stenosis. He underwent angioplasty for recurrence of the stenosis and consented to minimally invasive coronary artery bypass grafting. This technique greatly reduces the postoperative morbidity and minimizes complications of the surgery. The technique is probably a more definitive treatment than angioplasty or medical strategies.
Objectives This study investigated the efficacy of human skeletal myoblasts (SkM) mediated either human vascular endothelial growth factor-165 (hVEGF165) or angiopoietin-1 (Ang-1) on vascular development and myocardial regional perfusion. Methods A porcine heart model of chronic infarction was created in 28 female swine by coronary artery ligation. The animals were randomized into: (1) group-1, DMEM injected (n=6), (2) group-2, Ad-null transduced SkM transplanted (n=6), (3) group-3, Ad-hVEGF165 transduced SkM transplanted (n=8), and (4) group-4, Ad-Ang-1 transduced SkM (n=8). Three weeks later, 5 ml DMEM containing 3×108 SkM carrying exogenous genes were intramyocardially injected into 20 sites in left ventricle in groups-2, -3 and -4. Animals in group-1 were injected 5 ml DMEM without cells. Animals were kept on 5 mg/kg cyclosporine per day for 6 weeks. Regional blood flow was measured using fluorescent microspheres. The heart was explanted at 2, 6 and 12 weeks after transplantation for histological studies. Results Histological examination showed survival of lac-z expressing myoblasts in host tissue. Capillary density based on Von Willebrand factor-VIII (vWF-VIII) at low power field (×100) was 57.13±11.85 in group-3 at 6 weeks and declined to 32.1±5.21 at 12 weeks, while it was 39.9±10.26 at 6 weeks and increased to 45.14±6.54 at 12 weeks in group-4. The mature blood vessel index was highest in group- 4 at 6 and 12 weeks after transplantation. The regional blood flow in the center and peri-infarct area was significantly increased in animals of groups-3 and -4. Conclusions SkM carrying either hVEGF165 or Ang-1 induced neovascularization with increased blood flow. Ang-1 overexpression resulted in mature and stable blood vessel formation and may be a more potent arteriogenic inducer for neovascularization.
Human Myoblast Genome Therapy (HMGT) is a platform technology of cell transplantation, nuclear transfer, and tissue engineering. Unlike stem cells, myoblasts are differentiated, immature cells destined to become muscles. Myoblasts cultured from satellite cells of adult muscle biopsies survive, develop, and function to revitalize degenerative muscles upon transplantation. Injection injury activates regeneration of host myofibers that fuse with the engrafted myoblasts, sharing their nuclei in a common gene pool of the syncytium. Thus, through nuclear transfer and complementation, the normal human genome can be transferred into muscles of patients with genetic disorders to achieve phenotype repair or disease prevention. Myoblasts are safe and efficient gene transfer vehicles endogenous to muscles that constitute 50% of body weight. Results of over 280 HMGT procedures on Duchenne Muscular Dystrophy (DMD) subjects in the past 15 years demonstrated absolute safety. Myoblast-injected DMD muscles showed improved histology. Strength increase at 18 months post-operatively averaged 123%. In another application of HMGT on ischemic cardiomyopathy, the first human myoblast transfer into porcine myocardium revealed that it was safe and effective. Clinical trials on approximately 220 severe cardiomyopathy patients in 15 countries showed a 10% mortality. Most subjects received autologous cells implanted on the epicardial surface during coronory artery bypass graft, or injected on the endomyocardial surface percutaneously through guiding catheters. Significant increases in left ventricular ejection fraction, wall thickness, and wall motion have been reported, with reduction in perfusion defective areas, angina, and shortness of breath. As a new modality of treatment for disease in the skeletal muscle or myocardium, HMGT emerged as safe and effective. Large randomized multi-center trials are under way to confirm these preliminary results. The future of HMGT is bright and exciting.
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