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Platelet and neutrophil interactions with injured vascular wall may contribute to restenosis. Their importance was mainly examined following balloon injury of intact arteries. However, dilation of diseased arteries is clinically more relevant and may elicit different responses. We investigated the relationship between platelets and neutrophil adhesion, neointima formation and P-selectin expression on damaged arteries after repeated balloon injury. In an acute single-injury model, 8 pigs were subjected to bilateral carotid angioplasty and sacrificed 1 h later. In a chronic model, 19 pigs were subjected to similar procedures and allowed to recover for 4 weeks; then 18 arteries were redilated at the same previously injured sites (double injury) while the remaining arteries were not redilated and used to investigate the extent and the adhesive properties of the neointima. After single injury, 51Cr-platelet adhesion (×106/cm2) increased significantly from 3.8 ± 0.6 to 45.9 ± 6.5 (p < 0.05) on mildly and deeply injured segments, respectively, and were statistically similar after double injury. After single injury, 111In-neutrophil adhesion (×103/cm2) increased from 226.6 ± 45.5 to 512.5 ± 70.3 (p < 0.05) on mildly and deeply injured segments, and were significantly higher (p < 0.05) after double injury (mild: 1,289.1 ± 227.9 and deep: 2,411.8 ± 333.9). As well, the neo-endothelium expresses P-selectin at 4 weeks and platelet and neutrophil adhesion was directly related to neointimal growth. These results, which indicate ongoing proinflammatory processes 1 month post-angioplasty, suggest that neutrophils may participate in the progression of restenosis.

Preclotting is mandatory prior to implanting a knitted polyester arterial graft, unless the structure is made impermeable to blood by coating with a bioerodible material. Before achieving wide-spread clinical acceptance, the technique of impregnating with cross-linked albumin must be optimized in order to develop a graft that is immediately implantable, easy to handle and suture and has improved healing characteristics. The choice of the chemical to cross-link the albumin is of paramount importance. In this study two alternative candidates have been evaluated by using a series of tests to measure the physical properties, the morphology and the cytocompatibility of albumin-coated grafts. A carbodiimide cross-linking agent appears more promising than glutaraldehyde, since it is equally effective in producing a blood impermeable prosthesis, yet presents improved biocompatibility and provokes a less intense inflammatory response from the host.

Previous in vitro studies have predicted that the type of chemical used to cross-link albumin-coated polyester arterial prostheses may influence the rate of bioerosion of the albumin layer in vivo. This study has confirmed that the healing process of this type of compound prosthesis does indeed depend on the nature and concentration of the cross-linking agent used. Four series of implantations in the thoracic aorta of dogs for scheduled periods for 4 h up to 6 months were conducted using 1.6% glutaraldehyde, 2.5% glutaraldehyde and 0.2 M carbodiimide as the alternative cross-linking agents plus a nonalbuminated preclotted polyester prosthesis which served as the control. The pathology of the explanted grafts revealed that in the short and medium term the rate of healing and the extent of tissue ingrowth was dependent initially on the presence of and later on the rate of bioerosion of the albumin layer. After 3 months in situ, the prostheses coated with albumin cross-linked with 1.6% glutaraldehyde and carbodiimide had healed more rapidly and were invaded by more extensive tissue ingrowth than the one cross-linked with 2.5% glutaraldehyde or the preclotted control. Moreover, the migration of cells over the carbodiimide-treated surface was the most fully developed and most regularly organized of all four series. Immunostaining revealed that the presence of glutaraldehyde induced an inflammatory response which failed to support the growth of normal luminal cells with the endothelial phenotype.