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J Thorac Cardiovasc Surg 1996;111:678-680
© 1996 Mosby, Inc.
BRIEF COMMUNICATIONS |
Milwaukee, Wis.
From the Milwaukee Heart Project, Milwaukee, Wis.
Received for publication July 19, 1995 Accepted for publication Sept. 5, 1995.
To date, dynamic cardiomyoplasty relies on use of a properly conditioned, adequately contracting autogenous muscle flap for the correction of myocardial insufficiency. Despite its advantages, cardiomyoplasty has some unresolved problems: (1) poor angiogenic potential of the ischemic, traumatized skeletal muscle and damaged myocardium and (2) incomplete contact between the mobile myocardial wall and the transplanted flap. These problems manifest themselves after the opertion. The vascular supply is not reintroduced until 6 to 8 months after the operation. Some patients have died of recurrent myocardial infarction 3 to 5 months after cardiomyoplasty, before a new blood supply from the skeletal muscle to the myocardium had been established.
1,2 This is the situation that needs to be resolved. Cardiomyoplasty done with skeletal muscle can provide capillary ingrowth to the myocardium, but it may be too late for some patients.
A novel approach to resolving these problems involves "therapeutic angiogenesis." Nine weeks after a modified fibrin glue (containing endothelial cell growth factor) has been applied between the aorta and the left ventricular myocardium, angiographic and histologic investigations have shown newly grown vascular structures between these sites. 3 The results of this study confirm previous observations that site-directed neovessel formation can be induced by application an angiogenic growth factor. 4,5
We have implemented the idea of using biologic glue based on a fibrinogen-thrombin composition for cardiomyoplasty. Fibrinogen, the main component of biologic glue, was prepared from donor animals by a standard cryoprecipitation technique. In brief, whole blood obtained from the donor was centrifuged and the plasma decanted. After the plasma had been frozen for 12 hours at -80° C, it was thawed at 4° C for 4 hours and then centrifuged. The yellowish white precipitate that remained after decantation was collected and stored at -18° C. The resulting cryoprecipitate contained concentrated fibrinogen, factor XIII, fibronectin, and vitronectin. In other experiments pure fibrinogen from sheep plasma (F-9754, Sigma Chemical Company, St. Louis, Mo.) was used. Thrombin was purchased from Johnson & Johnson Patient Care, Inc. (New Brunswick, N.J.). In both cases, final solutions of fibrinogen and thrombin were prepared in separate delivery systems. After mobilization of the latissimus dorsi muscle in adult sheep, the muscle was introduced into the thoracic cavity and wrapped around the heart. The muscle flap was sutured to the myocardium of the left ventricle and two isolated pockets were created. In one of the pockets the biologic glue was introduced by simultaneously applying the two separate solutions of fibrinogen and thrombin between the skeletal muscle and myocardium. The amount of glue used per animal was in the range of 20 to 30 ml. As a control, no biologic glue was introduced in the other pocket. After the operation the animals had the usual postoperative management and the typical stimulation protocol for skeletal muscle training.
After 8 weeks we examined the muscle flap and the myocardium of the left ventricle (Fig. 1). We saw extremely strong adhesions between the latissimus dorsi muscle and the myocardium in the pocket where the biologic glue had been applied. Histologic examination showed new blood vessel growth of significant diameter (Fig. 2). No adhesions had developed in the areas in which biologic glue was not used.
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Enhancement of angiogenesis and vasculogenesis after cardiomyoplasty might be achieved by local implantation of autologous endothelial cells cultured ex vivo or by application of angiogenic factors like vascular endothelial growth factor, platelet-derived growth factor, insulin-like growth factor, fibroblast growth factor, or extracellular matrix components like fibronectin, laminin, and proteoglycans. From this point of view, the fibrin meshwork serves only as a local delivery depot. However, it seems to us that a pure fibrin meshwork can sufficiently mimic the extracellular matrix for endothelial cells and support their growth. We believe that further study is required to assess the potential of various growth factors and suppressors of ischemia- reperfusion lesions in shortening the recovery period between surgery and full assistance in pumping functions of the native heart.
Footnotes
J THORAC CARDIOVASC SURG 1996;111:678-80 
References
This article has been cited by other articles:
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 V. S. Chekanov, V. Nikolaychik, M. A. Maternowski, R. Mehran, M. B. Leon, M. Adamian, J. Moses, G. Dangas, N. Kipshidze, and M. Akhtar Deferoxamine enhances neovascularization and recovery of ischemic skeletal muscle in an experimental sheep model Ann. Thorac. Surg., January 1, 2003; 75(1): 184 - 189. [Abstract] [Full Text] [PDF]
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