Evaluation of a Bovine Vascular Graft in Sheep.

The study objective was to determine safety and efficacy of a treated bovine vascular xenograft, in two Good Laboratory Practice compliant studies in sheep following carotid graft implantation. In one study, a 3- to 5-mm diameter xenograft was implanted into the right carotid artery of male sheep and compared to autologous jugular vein and a polymeric grafts similarly implanted. In a second study, a 9.5- to 14-mm diameter xenograft similarly implanted into the right carotid artery was compared to an autologous saphenous vein. Monthly Doppler ultrasound evaluation of implant patency and flow in implants and contralateral control carotid arteries was performed. The small vessel cohort 6 month xenograft patency was equivalent (or better) than animals with polymeric vascular graft or autologous vein implants; the aneurysm incidence was less than that of autologous vein grafts. In the large vessel cohort, all 15 xenografts and 12/15 saphenous vein implants were patent at 6 month follow-up. Tissue histology showed mild inflammatory responses in the xenografts that was slightly greater than suture material. In summary, treated bovine xenograft performance in this small study suggests it may be superior to polymeric autologous vein grafts, and may have a similar failure rate as autologous vein grafts after implantation.

[Immunological aspects of formation of restenoses after endothelial lesions].

The article deals with an analysis of the literature data concerning immunological mechanisms of the formation of restenoses after damage of the arterial wall, considering the participants of the early and late phases of inflammatory response initiated by endothelial damage. Also given is characteristics of the process of formation on the neointima, followed by description of the role of intercellular adhesion molecules in initiation and maintaining of the processes of acute and chronic inflammation.

Vein graft harvesting induces inflammation and impairs vessel reactivity.

BACKGROUND: Saphenous veins are often used for coronary artery bypass grafting (CABG), but loss of patency is a problem. The surgical procedure may contribute to graft injury. Our aim was to study the impact of surgical handling of saphenous veins on graft inflammation and vascular function. METHODS: Biopsy samples of saphenous veins were taken from 9 patients undergoing elective CABG at the start of vein harvesting (open technique) and after the last proximal anastomosis was sutured. Messenger RNA was extracted and amplified with semiquantitative reverse transcription polymerase chain reaction. Gene expression of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta), leukocyte adhesion molecules (E-selectin, intercellular adhesion molecule-1), and vasoactive substances (endothelin-1, inducible and endothelial nitric oxide synthase) was investigated. Translocation of nuclear factor-kappaB (NFkappaB) was evaluated with electrophoretic mobility shift assay. Immunostaining for von Willebrand factor was performed to evaluate loss of endothelium, and in vitro vein reactivity to phenylephrine and endothelin-1 was studied. RESULTS: Gene expression of cytokines and leukocyte adhesion molecules increased after graft harvesting and storage, whereas vasoactive substances did not change. Nuclear translocation of NFkappaB occurred after surgical handling, concurrent with partial loss of endothelium and impaired contractile function. CONCLUSIONS: Standard surgical handling of vein grafts induces NFkappaB-driven inflammation in the vessel wall and impairs vascular function. This may potentially contribute to both early and late graft occlusion.

Targeting CCR2 or CD18 inhibits experimental in-stent restenosis in primates: inhibitory potential depends on type of injury and leukocytes targeted.

A central role for leukocytes in neointimal hyperplasia after arterial injury is suspected. However, the relative importance of neutrophils and monocytes in balloon or stent-induced injury are not well understood, and mechanistic targeting of leukocyte recruitment or function is crude. We determined the temporal and spatial distribution of different leukocytes after balloon and stent-induced injury in primate iliac arteries. Based on these data, we targeted neutrophil and monocyte recruitment selectively after angioplasty or stent implantation and demonstrated that monocyte-specific blockade achieved via blockade of the MCP-1 receptor CCR2, was effective at reducing neointimal hyperplasia after stenting. In contrast, combined neutrophil and monocyte blockade achieved by targeting the leukocyte beta(2)-integrin beta-subunit CD18 was required to reduce neointimal hyperplasia after balloon injury. Distinct patterns of leukocyte infiltration in balloon versus stent-injured arteries predict distinct mechanisms for antiinflammatory strategies targeting neutrophils or monocytes in primates and may assist design of effective clinical strategies for optimizing vascular interventions.