During the last several years, great advances have been made in our understanding of angiogenesis, the study of blood vessel growth and proliferation. Several of the agents which promote this process have been well characterized. One promising agent, endothelial cell growth factor (ECGF), has been synthesized through recombinant techniques. The purpose of this investigation is to utilize ECGF in a canine model to effect myocardial angiogenesis, and to direct this process to ameliorate myocardial ischemia. In our model, the left anterior descending coronary artery (LAD) of dogs is occluded gradually over a 2 to 3 week period by an ameroid device applied to the proximal vessel. The internal mammary artery (IMA) is implanted into the region normally supplied by the LAD. lt is known that collateral vessels develop from the IMA and other sources to supply the territory normally perfused by the LAD. Myocardial blood flow is generally sufficient under rest conditions, but is inadequate under conditions of stress. We have developed a means to quantitate the maximal conductance between the IMA and the LAD vascular bed, assessing myocardial perfusion, the physiologic result of angiogenesis. Ameroids will be applied to the LAD of 24 dogs. The IMA will be implanted in the LAD area. As heparin is known to stabilize ECGF and promote its effect, dogs will be randomly assigned to receive infusions of ECGF in heparin, heparin alone, or normal saline. After 8 weeks, resting and maximal myocardial blood flow will be quantitated using radiolabeled microspheres. The maximal IMA to LAD bed conductance will be calculated, and comparisons made between groups. In addition, the effect of IMA occlusion on regional left ventricular function will be assessed using sonomicrometry. Vessels will be examined morphometrically and various hematologic, biochemical, and immunologic parameters will be assessed in the 3 groups, to determine potential adverse effects of ECGF.
