Heparin accelerates coronary collateral development in a porcine model of coronary artery occlusion.

Abstract

BACKGROUND Coronary collaterals develop in response to an ischemic stimulus. However, collateral growth is not sufficient to result in the complete recovery of coronary reserves. Using a porcine model of gradual coronary artery occlusion, we investigated the effect of continuous heparin infusion on coronary collateral development. METHODS AND RESULTS We placed ameroid constrictors on the left circumflex coronary artery of 16 minipigs; the ameroid constrictors completely occluded the left circumflex coronary artery at 10 +/- 1 days. Half of the animals also were instrumented with subcutaneously placed osmotic pumps and catheters that delivered heparin (300 units/h) into the external jugular vein. At 2, 3, and 4 weeks, we assessed blood flow at rest and during vasodilation using radioactive microspheres. Our results indicate that the animals receiving heparin restored resting myocardial blood flow to normal levels at or before 2 weeks; in contrast, we did not see normal resting myocardial blood flow levels in the untreated-ameroid animals until 3 weeks. Under vasodilated conditions, untreated-ameroid animals experienced a severe loss of coronary reserves at 2 weeks. Although this improved with time, these animals still were significantly underperfused at 4 weeks. In contrast, in the heparin-treated animals, coronary reserves returned to near-normal levels between 3 and 4 weeks. In addition, infarct size was significantly smaller in the heparin-treated animals. CONCLUSIONS These experiments suggest that the administration of heparin in the early phases of gradual coronary occlusion accelerates the rate of return of normal blood flow under resting conditions, substantially increases the recovery of coronary reserve, and reduces the risk of infarction.