An ultrastructural study of progressive intimal hyperplasia in rat vein grafts.

Abstract

Intimal hyperplasia (IH) poses the greatest challenge for vein graft success. This fibroproliferative disorder causes obliterative stenosis and frequent graft occlusion. Although its causes remain poorly understood, it has been proposed that IH begins as a wound-healing response that cascades into a chronic state of unchecked proliferation. In this ultrastructural study, IH development and concomitant cell changes were evaluated in rat vein grafts. Epigastric vein-to-femoral artery grafts were placed in Lewis rats using standard microsurgical techniques. At various time points, grafts were harvested and processed for transmission electron microscopic, histologic, and immunohistochemical analyses. The proximal region, which displayed the most marked IH, was assessed for ultrastructural changes. Our findings showed: (1) regeneration of the damaged endothelium by cells displaying an activated appearance; (2) early and complete smooth muscle cell death, with subsequent replacement by myofibroblastic cells; (3) extensive and sustained graft infiltration by monocytes/macrophages; and (4) intramural fibrin deposition. The rat vein graft wall was substantially altered after implantation into the arterial circulation. During and after IH development, the cells in the graft did not resemble cells that are present in the nongrafted epigastric vein. Marked cell death, mononuclear cell infiltration, and the presence of myofibroblastic cells suggest a state of aberrant wound healing.