Heparin potentiates collateral growth but not growth of intramyocardial endarteries in dogs with repeated coronary occlusion

Heparin accelerates coronary collateral development in various animal models of myocardial ischemia. The purpose of this study was to clarify the beneficial effect of heparin on canine collateral development. Seventeen adult mongrel dogs were instrumented for measurements of a subendocardial segment length in the central area perfused by the left circumflex coronary artery, its flow, and left ventricular pressure. A pulsed Doppler flow probe and an externally inflatable pneumatic occluder were placed around the proximal circumflex artery. After the recovery from surgery, 2-min circumflex coronary artery occlusions were repeated eight times at 58-min intervals daily. After excluding seven dogs with well-developed preexisting collateral circulation, ten dogs were randomized into two groups with (n=5) and without (n=5) heparin treatment. The total occlusion time until adequate collateral development (an index of collateral growth) was 164±34 (SD) min in dogs with heparin treatment, being significantly less than 289±49 min in dogs without heparin (p<0.01). In contrast, the extent of the reduction in resting blood flow of the repeatedly occluded circumflex artery (an index of neovascularization toward the ischemic area) was comparable in dogs with and without heparin (15.4±12.4% vs. 21.1±13.6%, p=NS). Heparin promotes nonsprouting angiogenesis (arteriogenesis) of preformed collateral vessels but not neovascularization toward the ischemic area in dogs with brief repetitive coronary occlusions.