Creating molecular barriers to acute platelet deposition on damaged arteries with reactive polyethylene glycol

We report here a novel method for blocking acute platelet deposition at the site of vessel injury by molecularly masking thrombogenic vascular wall proteins with covalently attached polyethylene glycol (PEG). To evaluate this technique, blood containing 111In-labeled platelets was perfused over damaged human placental arteries for 2 min at a wall shear rate of 200 s-1. Denuded vessel segments were incubated for 30, 15, 5, and 1 min with a solution of either reactive PEG-diisocyanate (PEG-ISO) or nonreactive PEG-dihydroxyl (PEG-OH). Vessels treated with PEG-ISO for 1 min exhibited 87 +/- 12% less platelet deposition (p < 0.01) than untreated control vessels, and this reduction did not vary significantly among treatment times, indicating that this reaction occurs rapidly enough to be clinically applicable. To investigate the duration of this thrombotic barrier, denuded pig carotid arteries were treated with reactive PEG-ISO for 1 min, perfused with plasma for 30 min, and then perfused with blood containing radiolabeled platelets. PEG-ISO-treated arteries exhibited 84 +/- 9% less platelet deposition (p < 0.05) than untreated controls. These data demonstrate that damaged arterial surfaces can be rendered resistant to platelet deposition after short contact periods with reactive PEG. Molecular PEG barriers ultimately might find application following vascular procedures to sterically inhibit blood cell interaction with damaged vascular surfaces.