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Ann Thorac Surg 1999;68:1924-1928
© 1999 The Society of Thoracic Surgeons

I. Pathophysiology of Ischemic Reperfusion Injury

Myocardial protection: is there a role for gene therapy?

Margaret D. Allen, MDa

a Division of Cardiothoracic Surgery, University of Washington, Seattle, Washington, USA

Address reprint requests to Dr Allen, Division of Cardiothoracic Surgery, University of Washington, Mailstop 356310, 1959 NE Pacific St, Seattle, WA 98195
e-mail: allenm{at}ctd.surgery.washington.edu

Presented at the International Symposium on Myocardial Protection From Surgical Ischemic-Reperfusion Injury, Asheville, NC, Sep 21–24, 1997.

Abstract

Modification of gene expression within the heart could have a dramatic impact on both cardiac transplantation and routine cardiac surgery within the next decade. The advantage of gene therapy is that it would allow organ-selective local delivery of higher levels of cytokines, growth factors, vasodilators, or immunosuppressive drugs than could be safely achieved by systemic administration. Direct transfection or transduction of myocytes, endothelium, and/or vascular smooth muscle cells could increase the density of beta adrenergic receptors, inhibit endothelial adhesion molecule expression, or prevent neointimal formation in coronary bypass grafts. Cell transfer of neonatal or engineered adult myocytes might allow repopulation of infarct areas. The current limitations to effective clinical gene therapy are the variable transfection efficiencies of gene delivery systems, limited duration of gene expression, immune responses to viral vectors, and safety concerns. Ischemia-reperfusion injury will be one of the earliest applications for gene therapy since the short time course of injury and recovery would be amenable to therapeutic approaches with limited durations of action, achievable by currently available delivery vectors.




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[Abstract] [Full Text] [PDF]


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