Myocardial protection: Is there a role for gene therapy?

Modification of gene expression within the heart could have a dramatic impa ct on both cardiac transplantation and routine cardiac surgery within the n ext decade. The advantage of gene therapy is that it would allow organ-sele ctive local delivery of higher levels of cytokines, growth factors, vasodil ators, or immunosuppressive drugs than could be safely achieved by systemic administration. Direct transfection or transduction of myocytes, endotheli um, 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 ne onatal or engineered adult myocytes might allow repopulation of infarct are as. The current limitations to effective clinical gene therapy are the vari able transfection efficiencies of gene delivery systems, limited duration o f gene expression, immune responses to viral vectors, and safety concerns. Ischemia-reperfusion injury will be one of the earliest applications for ge ne therapy since the short time course of injury and recovery would be amen able to therapeutic approaches with limited durations of action, achievable by currently available delivery vectors. (C) 1999 by The Society of Thorac ic Surgeons.