One of the major problems in cardiology today is how to more effectively treat individuals with coronary artery disease who have symptoms refractory to conventional therapy, including antianginal drugs and coronary artery bypass surgery. One potential approach we are currently investigating is implantation of the internal mammary artery (IMA) into ischemic regions of the left ventricle. This operation has been performed on patients in the past, but the blood flow through the IMA has been found to be generally insufficient, incapable of delivering enough blood flow to importantly influence symptoms. Heparin, a commonly utilized anticoagulant, has been found to play a major role in the process of angiogenesis, the formation of new blood vessels, in vitro. This experiment is designed to assess the ability of heparin to potentiate the growth of vascular connections derived from the IMA when implanted in ischemic myocardium in a canine model. Foxhounds will undergo IMA implantation into the anterior wall of the left ventricle (Vineberg Procedure). Animals will randomly be assigned to receive continuous administration into the IMA of either heparin or normal saline (control group). The area of the left ventricle in which the IMA graft is placed will be rendered ischemic over a two to three week period by positioning an ameroid constrictor around the left anterior descending coronary artery. Animals will be studied eight weeks postoperatively to determine both the baseline myocardial blood flow and the maximum capacity for myocardial blood flow (vasodilator reserve) in the ischemic zone. The gross and microscopic distribution of vascular anastomoses as well as the density of capillaries within the ischemic area will subsequently be determined with a digital video analyzer and comparisons will be made between the heparin and control groups.
