The observation of intimal hyperplasia at bypass graft anastomoses has suggested a potential interaction between local hemodynamics and vascular wall response. Wall shear has been particularly implicated because of its known effects upon the endothelium of normal vessels and, thus, was examined as to its possible role in the development of intimal hyperplasia in arterial bypass graft distal anastomoses. Tapered (4-7 mm I.D.) e-PTFE synthetic grafts 6 cm long were placed as bilateral carotid artery bypasses in six adult, mongrel dogs weighing between 25 and 30 kg with distal anastomotic graft-to-artery diameter ratios (DR) of either 1.0 or 1.5. Immediately following implantation, simultaneous axial velocity measurements were made in the toe and artery floor regions in the plane of the anastomosis at radial increments of 0.35 mm, 0.70 mm, and 1.05 mm using a specially designed 20 MHz triple crystal ultrasonic wall shear rate transducer Mean, peak, and pulse amplitude wall shear rates (WSRs), their absolute values, the spatial and temporal wall shear stress gradients (WSSG), and the oscillatory shear index (OSI) were computed from these velocity measurements. All grafts were harvested after 12 weeks implantation and measurements of the degree of intimal hyperplasia (IH) were made along the toe region and the artery floor of the host artery in 1 mm increments. While some IH occurred along the toe region (8.35+/-23.1 microm) and was significantly different between DR groups (p<0.003), the greatest amount occurred along the artery floor (81.6+/-106.5 microm, mean +/- S.D.) (p < 0.001) although no significant differences were found between DR groups. Linear regressions were performed on the paired IH and mean, peak, and pulse amplitude WSR data as well as the absolute mean, peak, and pulse amplitude WSR data from all grafts. The mean and absolute mean WSRs showed a modest correlation with IH (r = -0.406 and -0.370, respectively) with further improvements seen (r = -0.482 and -0.445, respectively) when using an exponential relationship. The overall best correlation was seen against an exponential function of the OSI (r = 0.600). Although these correlation coefficients were not high, they were found to be statistically significant as evidenced by the large F-statistic obtained. Finally, it was observed that over 75 percent of the IH occurred at or below a mean WSR value of 100 s(-1) while approximately 92 percent of the IH occurred at or below a mean WSR equal to one-half that of the native artery. Therefore, while not being the only factor involved, wall shear (and in particular, oscillators wall shear) appears to provide a stimulus for the development of anastomotic intimal hyperplasia.

Controlled release of microgram quantities of VEGF significantly enhanced neovascularization and vascular perfusion in ischemic limbs compared with controls in this rabbit model of partial ischemia. In addition, VEGF-treated ischemic limbs demonstrated near-normal function and appearance, whereas NTG- and saline-treated ischemic controls remained noticeably impaired. This novel approach of VEGF delivery may prove clinically useful either alone or combined with revascularization procedures.

Residues from hydrocolloid dressings (HCDs) that originate from matrix disintegration and nonbiodegradability of the absorbent components, may cause deep-seated, unresolved inflammation in tissue that appears otherwise healed. The purpose of this study was to evaluate three new HCDs that were formulated with the goal of attenuating the inflammatory responses that may arise from HCD therapy. Two of the HCDs (A-106 and A-107) consisted of conventional absorbents dispersed in a new maceration-resistant adhesive matrix. The same matrix, mixed with potentially biodegradable dextran microspheres, formed the third dressing (Dextran Bead Dressing [DBD]). In this pilot scale study these novel dressings were evaluated on full-thickness dermal wounds on swine. Restore (Hollister) and DuoDERM CGF (Convatec) dressings were used as controls. Wound healing was evaluated histomorphometrically. Pertinent histologic parameters were ranked from wound tissue that was harvested 18 days after wounding. Grossly visible dressing disintegration ranged from minimal (DBD) to severe (Restore). Disintegration of other dressings was moderate. The percentage of tissue sections exhibiting giant cells reflected, in parallel, the observed extent of dressing disintegration. Thirty-eight percent of wounds dressed with DBD contained giant cells; 74 and 100% of wounds treated with DuoDERM CGF and Restore, respectively, contained giant cells. DBD-dressed wounds had relatively fewer chronic inflammatory cells than other dressings. These wounds were also characterized by a well-organized collagen matrix and complete reepithelialization. The extent of wound closures was similar for all dressing types except Restore. Closure of Restore-dressed wounds was delayed compared with closure with DBD and DuoDERM CGF on all days of evaluation except one. A-106 and A-107 were comparable to DuoDERM CGF in retention of dressing integrity and the elicited inflammatory tissue response. The DBD dressing appears to possess equivalent properties of typical HCDs while causing minimal tissue reactions.

The presence of electrostatic EC seeding significantly (p < 0.01) enhanced the development of a neointima and reduced the incidence of thrombosis in e-PTFE grafts implanted in a canine femoral artery model. Results of the mid-graft SMC migration measurements indicate that the electrostatic EC seeding had a significant (p < 0.001) impact on the acute healing of the standard wall e-PTFE vascular graft specimens.

Wall shear has been widely implicated as a contributing factor in the development of intimal hyperplasia in the anastomoses of chronic arterial bypass grafts. Earlier studies have been restricted to either: (1) in vitro or computer simulation models detailing the complex hemodynamics within an anastomosis without corresponding biological responses, or (2) in vivo models that document biological effects with only approximate wall shear information. Recently, a specially designed pulse ultrasonic Doppler wall shear rate (PUDWSR) measuring device has made it possible to obtain three near-wall velocity measurements nonintrusively within 1.05 mm of the vessel luminal surface from which wall shear rates (WSRs) were derived. It was the purpose of this study to evaluate the effect of graft caliber, a surgically controllable variable, upon local hemodynamics, which, in turn, play an important role in the eventual development of anastomotic hyperplasia. Tapered (4-7 mm I.D.) 6-cm-long grafts were implanted bilaterally in an end-to-side fashion with 30 deg proximal and distal anastomoses to bypass occluded common carotid arteries of 16 canines. The bypass grafts were randomly paired in contralateral vessels and placed such that the graft-to-artery diameter ratio, DR, at the distal anastomosis was either 1.0 or 1.5. For all grafts, the average Re was 432 +/- 112 and the average Womersley parameter, alpha, was 3.59 +/- 0.39 based on artery diameter. There was a sharp skewing of flow toward the artery floor with the development of a stagnation point whose position varied with time (up to two artery diameters) and DR (generally more downstream for DR = 1.0). Mean WSRs along the artery floor for DR = 1.0 and 1.5 were found to range sharply from moderate to high retrograde values (589 s-1 and 1558 s-1, respectively) upstream to high antegrade values (2704 s-1 and 2302 s-1, respectively) immediately downstream of the stagnation point. Although there were no overall differences in mean and peak WSRs between groups, there were significant differences (p < 0.05) in oscillatory WSRs as well as in the absolute normalized mean and peak WSRs between groups. There were also significant differences (p < 0.05) in mean and peak WSRs with respect to axial position along the artery floor for both DR cases. In conclusion, WSR varies widely (1558 s-1 retrograde to 2704 s-1 antegrade) within end-to-side distal graft anastomoses, particularly along the artery floor, and may play a role in the development of intimal hyperplasia through local alteration of mass transport and mechano-signal transduction within the endothelium.