Endothelial Loss due to Leukocytes in Canine Experimental Vein-to-Artery Grafts

Abstract

Vein-to-artery grafts develop areas of endothelial loss with fibrin and leukocytes which lead to early thrombosis and may lead to subsequent atherosclerosis of the graft. En face monolayers were prepared which removed >90% of vascular intima. Unevenly distributed leukocytes and endothelial cells were counted using a standardized sampling of calibrated oil immersion fields of 0.01 mm2. Nongrafted veins had 14 ± 1 evenly arranged endothelial cells per field without gaps or leukocytes, while 10-min grafts had 13 ± 2 with rare leukocytes. Four-hour grafts from normal dogs had 9 ± 2 endothelial cells with gaps and 97 ± 37 neutrophils and 44 ± 25 monocytes. Leukopenic dogs (vinblastine-treated) had normal numbers of endothelial cells (14 ± 1) with scanty leukocytes. We conclude that leukocytes cause endothelial loss in vein-to-artery grafts that can be prevented by intense leukopenia. This may lead to practical approaches to protecting such grafts in humans.

Perivenous support reduces early changes in human vein grafts: Studies in whole blood perfused human vein segments

“…This is in accordance with the animal studies. 10,22 Here we report the early effect of nonpulsatile perfusion of human vein segments in vitro with autologous whole blood and with arterial pressure. We describe the pathologic findings in the vein wall and the effect of perivenous stenting during the first hour of perfusion.…”

Vein graft failure: current clinical practice and potential for gene therapeutics

“…35 Endothelial denudation allows platelet and leukocyte adhesion immediately after graft implantation that precipitates thrombosis, as well as acting as an initiating factor for intimal thickening. [36][37][38][39] Adherent (activated) platelets generate a large number of substances, including thromboxane A 2 , endothelin-1, serotonin, platelet-derived growth factor, platelet factor IV, fibrinogen, fibronectin, thrombospondin, von Willebrand factor, b-thromboglobulin and reactive oxygen species, which activate VSMCs in the medial layer of the vein graft. Activated VSMCs are more synthetic and have heightened proliferation and migration rates (for a review, see Owens et al 40 ).…”

“…44 Leukocytes (neutrophils and monocytes) also participate in the induction of intimal thickening in the vein graft. [37][38][39] Adherent leukocytes, particularly neutrophils, release numerous pro-inflammatory substances, including leukotrienes, interleukins, histamine, tumour necrosis factor, platelet activating factor and proteases, all of which promote VSMC proliferation and migration (for a review, see Segel et al 45 ). Monocyte adhesion also occurs early after vein graft implantation and promotes intimal thickening.…”

The Pathobiology of Endothelin-1 in Vein Graft Disease: Are ETA Receptor Antagonists the Solution to Prevent Vein Graft Failure?

“…The adhesion of platelets and leukocytes is therefore an immediate occurrence following graft implantation which may not only precipitate thrombosis but also trigger NI formation [26][27][28][29] (Fig. 1).…”

“…Neutrophils and monocytes also promote NI formation [27,28,[33][34][35][36][37][38]. Adherent leukocytes, especially neutrophils, release an array of pro-inflammatory substances, including ET-1 [39].…”