Arterial response to mild balloon injury in the normal rabbit: evidence for low proliferation rate in the adventitia

Background The role of constrictive remodeling, spasm and proliferation (pa rticularly in the adventitia) in the genesis of chronic lumen narrowing aft er balloon injury remains under debate. This study analyzed the time course of these components following mild injury in normal arteries. Methods Iliac injury was induced by balloon overstretch in 32 rabbits, sacr ificed at timed intervals from day 3 to 28, Angiographic response to nitrat es, morphometric, immunohistochemical and biochemical analysis were perform ed at each time point. Results Quantitative angiography showed a decrease in lumen diameter and no change in response to nitrates over time. On morphometric analysis, remode ling was usually constrictive, appeared as early as day 3 and was responsib le for 69 +/- 14% of the histologic lumen area stenosis at day 28. Constric tive remodeling was correlated negatively to intimal hyperplasia (r = 0.51, P < 0.002) and positively to the lumen area stenosis (r = 0.92, P < 0.0001 ). Macrophages (labeled by anti-RAM 11 antibodies) were very rare at all ti me points. Immunohistochemistry identified a high rate of proliferating smo oth muscle cells in the media (13 +/- 7%) and intima (49 +/- 8%) at day 7, which decreased rapidly, Proliferating cells in the adventitia were rare (3 +/- 2% at day 7), The number of proliferating cells was time-dependent (r = 0.82, P < 0.0001) and related to cyclin A mRNA measured by reverse transc ription-polymerase chain reaction (r = 0.84, P < 0.0001). Conclusions In this model, luminal loss was mainly caused by constrictive r emodeling rather than intimal hyperplasia. Constrictive remodeling appeared early and was not time-dependent. Macrophages, spasm and adventitial proli feration did not contribute to this constrictive remodeling. Coronary Arter y Dis 9:805-814 (C) 1998 Lippincott Williams & Wilkins.