A novel organ culture method to study intimal hyperplasia at the site of acoronary artery bypass anastomosis

Background. Intimal hyperplasia or restenosis at the site of a coronary art ery bypass anastomosis contributes to early graft failure, and growth facto r release in response to construction of the anastomotic site strongly infl uences this process. Due to the difficulties in studying restenosis after c oronary artery bypass graft surgery, we have tested whether an organ cultur e model we have developed can simulate the early events associated with int imal hyperplasia. Methods. End-to-side anastomosis of porcine radial artery to porcine corona ry artery were constructed. The vessels were trimmed and incubated under st andard tissue culture conditions for 14 days. Appropriate controls were tre ated similarly. The vessels were frozen, cryosectioned, and immunostained f or the expression of the proliferation marker proliferating cell nuclear an tigen (PCNA). A proliferative index (PCNA positive nuclei/total nuclei) was calculated for comparative purposes. Results. Limited PCNA staining was observed in noncultured vessel segments (0.046 +/- 0.045). A slight increase in this index was observed in vessels that had been placed into culture without manipulation (0.230 +/- 0.141) an d in vessels subjected to an arteriotomy (0.462 +/- 0.249). However, the mo st significant increase was obtained after construction of an anastomosis ( 4.98 +/- 6.66). No change in total cell number was evident over the course of the experiment or in relation to the treatment. Conclusions. Culture conditions and incision slightly stimulate cell prolif eration in porcine coronary artery segments when compared with basal condit ions of a native artery. In contrast, construction of an anastomosis increa ses proliferation 108-fold. Therefore, surgical manipulation of arterial co nduits during construction of an anastomotic site is the primary trigger fo r intimal hyperplasia, independent of dissection and incision of the vessel . Furthermore, these data indicate the organ culture model we have develope d will be useful for examining the cellular and molecular mechanisms that m ediate intimal hyperplasia at the site of a coronary artery bypass graft an astomosis. (C) 2001 by The Society of Thoracic Surgeons.