Angioplasty/stents and coronary artery bypass grafting remain the primary interventional therapies for the treatment of coronary artery disease CAD, but these treatments remain limited by recurrent disease, significant associated morbidities and mortality, and the failure of these "mechanical" techniques to treat diffuse and small vessel disease. Gene therapy for angiogenesis describes an alternative revascularization strategy whereby angiogenic genes are delivered to ischemic tissues for the purpose of inducing neovascularization. To avoid the limitations of patients acting as their own controls used in previous clinical trials examining this therapy for the treatment of CAD, we designed a prospective, placebo controlled, blinded, randomized phase I/II trial to examine the consequence of adenovirus (Ad) vector-mediated myocardial transfer of the human vascular endothelial growth factor 121 cDNA (Ad_CUVEGF121.1), as compared to saline injection, as an adjunct in individuals undergoing "off-pump" coronary artery bypass (OPCAB) grafting to the left anterior descending " the right coronary artery. The Ad_CUVEGF121.1 vector (10⁹ particle units in 30, 100 l aliquots) or saline will be administered to the circumflex distribution. The underlying hypothesis is that direct administration to the myocardium of Ad_CUVEGF121.1 is safe and improves cardiac perfusion and function, This randomized, blinded, placebo controlled study design, in which angiogenic gene therapy is delivered in a consistent fashion and assessed by exercise testing, sestamibi SPECT scanning, and MRI without the potential toxicity induced by cardiopulmonary bypass, should allow the assessments of the two specific hypotheses: (1) there are no adverse effects in administering the Ad_CUVEGF121.1 vector in this fashion: and (2) there are global and/or regional improvements in cardiac perfusion and function associated with Ad_CUVEGF121.1 therapy. Because the study design is prospective, placebo controlled, blinded and randomized, the results should help determine whether larger trials of this therapy are warranted.