Abstract

The objective of this program project is to provide an understanding of the mechanisms of adaptation between a transplanted heart and the recipient, and to improve the long- term management of these individuals. The rationale for this work is that the current short-term management of such patients is reasonably satisfactory (one-year survival rates of approximately 80-90%), but there remain long- term problems such as accelerated atherosclerosis, myocardial fibrosis, hypertension and impaired renal function. Such problems are disorders of immunosuppression and adaptation, and an improved understanding of the physiologic and immunologic mechanisms of adaptation and maladaptation will provide the basis for improved patient care.
The specific aims are to study the processes of adaptation in cardiac transplantation in the following areas: 1. Physiologic Alterations A. Adrenergic Responsiveness and Receptor Function (Project 1) B. Cellular Electrophysiology and Pharmacology (Project 2) 2. Immunologic Alterations A. Studies in Adaptation in Experimental Cardiac Allografts and Xenografts (Project 3) B. Idiotypic Regulation of Allograft Immunity in Patients with Heart Transplants (Project 4) C. The Role of Cyclosporine Receptors in Cardiac Transplantation Project 5)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL036581-02
Application #
3098517
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1987-07-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027

  Publications

Shah, A S; Itescu, S; O'Hair, D P et al. (1996) Immunologic studies in primates undergoing concordant xenotransplantation as a bridge allotransplantation. Transplant Proc 28:745-6
Michler, R E; Shah, A S; Itescu, S et al. (1996) The influence of concordant xenografts on the humoral and cell-mediated immune responses to subsequent allografts in primates. J Thorac Cardiovasc Surg 112:1002-9
Shah, A S; Itescu, S; O'Hair, D P et al. (1996) Importance of cell-mediated immune responses in rejection of concordant heart xenografts in primates. Transplant Proc 28:775-6
Binah, O; Berke, G; Rosen, D et al. (1994) Calcium channel blockers modify electrophysiological effects induced by lytic granules from cytotoxic T lymphocytes in guinea pig ventricular myocytes. J Pharmacol Exp Ther 268:1581-7
Binah, O; Kline, R; Berke, G et al. (1993) Mechanisms whereby lytic granules from cytotoxic T lymphocytes damage guinea pig ventricular myocytes. Scand J Immunol 37:53-7
Pepino, P; Volpe, M; Rose, E A et al. (1992) Effect of complete cardiac denervation on atrial natriuretic factor release in baboons. J Surg Res 53:43-7
Binah, O; Marom, S; Rubinstein, I et al. (1992) Immunological rejection of heart transplant: how lytic granules from cytotoxic T lymphocytes damage guinea pig ventricular myocytes. Pflugers Arch 420:172-9
Cacalano, N A; Aggarwal, R; Quesniaux, V F et al. (1992) Novel monoclonal antibodies to cyclosporine A: characterization and epitope mapping with cyclosporine analogs and cyclophilin. Mol Immunol 29:107-18
Erlanger, B F (1992) Do we know the site of action of cyclosporin? Immunol Today 13:487-90
Cacalano, N A; Chen, B X; Cleveland, W L et al. (1992) Evidence for a functional receptor for cyclosporin A on the surface of lymphocytes. Proc Natl Acad Sci U S A 89:4353-7

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