Heparin promotes the formation of extracardiac to coronary anastomoses in a canine model.

We developed a canine model for the in vivo utilization of angiogenesis factors to promote revascularization of a collateral-dependent area of the heart and assessed the potential of heparin in this preparation. Ameroids were placed on the proximal left anterior descending coronary artery (LAD) of 29 dogs, and the left internal mammary artery (IMA) was implanted in an intramyocardial tunnel in proximity to the LAD. A tube positioned in the distal IMA provided a continuous retrograde infusion directly into the vessel from an implanted pump. Heparin (15 or 150 U/h) or saline vehicle was infused. After 8 wk, regional myocardial blood flow was assessed in the anesthetized state during adenosine-induced vasodilatation, before and during occlusion of the IMA. The IMA provided a greater proportion of maximal collateral flow in heparin-treated dogs (22 +/- 5%, n = 17) than in saline-treated dogs (9 +/- 2%, n = 12, P less than 0.05). Thus continuous infusion of heparin promotes the formation of collaterals between the extracardiac artery and the myocardial circulation, establishing the feasibility of targeting angiogenic agents for myocardial revascularization.