Related Experiment Videos
Heparin accelerates coronary collateral development in a porcine model of coronary artery occlusion
S M Carroll1, F C White, D M Roth
1Department of Pathology, University of California, San Diego, La Jolla.
Insights
Continuous heparin infusion accelerates coronary collateral development and improves blood flow recovery after gradual coronary artery occlusion. This treatment significantly enhances coronary reserve and reduces infarct size in a porcine model.
Area of Science:
- Cardiovascular research
- Ischemic heart disease
- Animal models
Background:
- Coronary collaterals develop in response to ischemia but are insufficient for full recovery.
- Gradual coronary artery occlusion is a model to study collateral growth.
- The role of heparin in enhancing collateral development is not fully understood.
Purpose of the Study:
- To investigate the effect of continuous heparin infusion on coronary collateral development in a porcine model of gradual coronary artery occlusion.
Main Methods:
- Minipigs underwent ameroid constrictors for gradual left circumflex coronary artery occlusion.
- Half of the animals received continuous heparin infusion (300 units/h).
- Myocardial blood flow and coronary reserves were assessed using radioactive microspheres at 2, 3, and 4 weeks.
Main Results:
- Heparin-treated animals restored resting myocardial blood flow by 2 weeks; untreated animals took 3 weeks.
- Coronary reserves returned to near-normal levels by 3-4 weeks in heparin-treated animals, versus significant underperfusion at 4 weeks in untreated animals.
- Heparin administration significantly reduced infarct size.
Conclusions:
- Early heparin administration accelerates resting blood flow recovery after gradual coronary occlusion.
- Heparin substantially improves the recovery of coronary reserve.
- Heparin reduces the risk of infarction in this model.
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.