REPEATED BALLOON INJURY OF RAT AORTA - A MODEL OF NEOINTIMA WITH ATTENUATED INHIBITION BY HEPARIN

Repeated arterial injury, because it challenges already activated cell s, may elicit a reaction that differs from that provoked by a single i njury. We compared the response of rat aorta to single and double ball oon injury and tested the inhibitory effect of heparin in both situati ons. For repeated injury, the first and second lesions were induced 3 weeks apart. Two weeks after repeated injury, the neointima that exist ed from the first lesion had expanded, with significant increases in i ntima-media wet weight and its DNA and elastin content and in the inti ma-to-media (I/M) thickness ratio. Two days after repeated injury, the expression of proliferating cell nuclear antigen (PCNA) was enhanced in both the media and the intima, indicating that cells from both laye rs are involved in the aortic response to a second lesion. As establis hed previously, treatment with heparin (continuous intravenous adminis tration, 50 IU/kg.h(-1)) almost totally suppressed the response to sin gle injury. However, heparin only attenuated the response to repeated injury, with a partial decrease in intima-media wet weight and its DNA and elastin content and in I/M thickness ratio. PCNA labeling showed that heparin inhibited the proliferative activity in medial cells much more strongly than in intimal cells. In conclusion, repeated aortic i njury elicits a reaction of both the media and preexisting neointima. In this mixed response, neointimal smooth muscle cells are less sensit ive than medial cells to inhibition by heparin, which results in a wea kened effect of the drug on the fibromuscular reaction.