Silyl-heparin bonding improves the patency and in vivo thromboresistance of carbon-coated polytetrafluoroethylene vascular grafts

AbstractObjectivesOur purpose was to improve the performance of carbon-coated expanded polytetrafluoroethylene vascular grafts by bonding the grafts with silyl-heparin, a biologically active heparin analog, using polyethylene glycol as a cross-linking agent.Material and methodSilyl-heparin–bonded carbon-coated expanded polytetrafluoroethylene vascular grafts (Bard Peripheral Vascular, Tempe, Ariz), were evaluated for patency and platelet deposition 2 hours, 7 days, and 30 days after graft implantation in a canine bilateral aortoiliac artery model. Platelet deposition was determined by injection of autologous, 111Indium-radiolabeled platelets, followed by a 2-hour circulation period prior to graft explantation. Histologic studies were performed on a 2-mm longitudinal strip of each graft (7-day and 30-day groups). Heparin activity of the explanted silyl-heparin grafts was determined by using an antithrombin-III based thrombin binding assay.ResultsOverall chronic graft patency (7-day and 30-day groups) was 100% for the silyl-heparin bonded (16/16) grafts versus 68.75% for control (11/16) grafts (P = .043). Acute 2-hour graft patency was 100% for the silyl-heparin bonded (6/6) grafts versus 83.3% for control (5/6) grafts. Radiolabeled platelet deposition studies revealed a significantly lower amount of platelets deposited on the silyl-heparin grafts as compared with control grafts in the 30-day group (13.8 ± 7.18 vs 28.4 ± 9.73, CPM per cm2 per million platelets, mean ± SD, P = .0451, Wilcoxon rank sum test). In the 2-hour group of dogs, a trend towards a lower deposition of platelets on the silyl-heparin grafts was observed. There was no significant difference in platelet deposition between the two grafts in the 7-day group. Histologic studies revealed a significant reduction in intraluminal graft thrombus present on the silyl-heparin grafts as compared with control grafts in the 30-day group of animals. In contrast, there was no difference in amount of graft thrombus present on both graft types in the 7-day group of dogs. Pre-implant heparin activity on the silyl-heparin bonded grafts was 2.0 IU/cm2 (international units[IU]/cm2). Heparin activity remained present on the silyl-heparin grafts after explantation at all 3 time points (2 hours: above upper limit of assay, upper limit = 0.57, n = 6; 7 days: 0.106 ± 0.015, n = 5; 30 days: 0.007 ± 0.001, n = 5; mean ± SD, IU/cm2).ConclusionSilyl-heparin bonding onto carbon-coated expanded polytetrafluoroethylene vascular grafts resulted in (1) improved graft patency, (2) increased in vivo graft thromboresistance, and (3) a significant reduction in intraluminal graft thrombus. This graft may prove to be useful in the clinical setting.AbstractClinical relevanceExpanded polytetrafluoroethylene (ePTFE) remains the most commonly used prosthetic graft material in infrainguinal arterial reconstructions. Reported long-term patency rates of ePTFE bypass grafts are inferior to those observed with autogenous vein. Modification of the luminal surface of ePTFE bypass grafts may prevent early graft failure and ultimately improve long-term graft performance. Silyl-heparin is a biologically active heparin analog that is readily adsorbed onto hydrophobic surfaces while retaining its anticoagulant properties. Silyl-heparin bonding onto carbon-coated ePTFE grafts improves the patency and in vivo thromboresistance and results in a decrease in intraluminal graft thrombus. This graft may be useful in the clinical setting

Binge ethanol prior to traumatic brain injury worsens sensorimotor functional recovery in rats.

A significant number of patients suffering from traumatic brain injury (TBI) have a high blood alcohol level at the time of injury. Furthermore, drinking alcohol in a binge-like pattern is now recognized as a national problem, leading to a greater likelihood of being injured. Our objective was to determine the consequences of a binge paradigm of alcohol intoxication at the time of TBI on long-term functional outcome using a sensitive test of sensorimotor function. We trained adult, male, Sprague Dawley rats on the skilled forelimb reaching task and then administered a single binge dose of ethanol (2 g/kg, i.p.) or saline for three consecutive days (for a total of 3 doses). One hour after the final ethanol dose, rats underwent a TBI to the sensorimotor cortex corresponding to the preferred reaching forelimb. Animals were then tested for seven weeks on the skilled forelimb reaching task to assess the profile of recovery. We found that the group given ethanol prior to TBI displayed a slower recovery curve with a lower recovery plateau as compared to the control group. Therefore, even a relatively short (3 day) episode of binge alcohol exposure can negatively impact long-term recovery from a TBI, underscoring this significant public health problem

A. Experimental design schematic.

<p>B. Representative kinematic sequence of a non-injured rat during the skilled reaching task. C. Fitted curves of the estimated group-level logistic recovery for rats given either three doses of binge ethanol (2g/kg) or vehicle control prior to TBI. The group differences in the midpoint (γ) and asymptote (α) of recovery were found to be statistically significant (p<.05).</p

A. Representative nissl stained coronal sections of saline treated and ethanol treated seven weeks post traumatic brain injury.

<p>The arrows indicate the location of the lesion. B. Lesion size expressed as a percent of the unlesioned hemisphere. No significant difference was found between saline and ethanol treated animals p>.05 (unpaired t-test). Error bars denote the ± SEM.</p