Platelet and fibrinogen turnover at the exposed subendothelium measured over 1 year after a balloon catheter de-endothelializing injury to the rabbit aorta: Thrombotic eruption at the late re-endothelialization stage

Balloon catheter de-endothelialization of the rabbit aorta in vivo causes a rapid release of thrombin and a consequent hemostatic response at the surface of the exposed subendothelium. Previously, we have compared the net fluxes of several hemostatic proteins from plasma into the exposed aorta subendothelium for up to 600 days after injury. We now report the turnover of platelets, compared to fibrinogen, at the de-endothelialized aorta for up to 390 days after injury. Anesthetized NZW rabbits received either a de-endothelializing or a sham injury (controls) to their aortas. At a predetermined time (either 10 min before or up to 390 days after injury), each rabbit was infused with known quantities of rabbit (51)Cr-platelets and rabbit (125)I-fibrinogen; the radiolabels were allowed to circulate for 10 min before the rabbit was rapidly exsanguinated. Radioactivity measurements and tissue analysis revealed that at 10 min after balloon injury, approximately 165,000 platelets/mm(2) were associated with the aorta surface, and platelet turnover was 840/min/mm(2). Turnover had decreased to <200/min/mm(2) at 10-21 days but, from 65 to 390 days, had increased to approximately 1500/min/mm(2). In comparison, approximately 17 pmol of fibrinogen/cm(2) saturated the ballooned surface by 10 min after injury. Fibrinogen turnover at the aorta surface at 10 min after injury amounted to 0.2 pmol/min/cm(2), increasing to 0.7 at 10 days but decreasing to 0.25 at 21 days. Between 65 and 390 days, fibrinogen turnover increased slowly to 1.3 pmol/min/cm(2). Fibrinogen turnover at the surface of the aorta paralleled that within the intima-media over 390 days. Platelet and fibrin(ogen) deposits within the aorta wall increased over the 21-390 days interval as shown by immunostaining. The results are consistent with the re-endothelializing aorta tending to support thrombosis and ulceration in the late healing stage.