Model system to study interaction of platelets with damaged arterial wall. I. Inhibition of platelet adhesion to subendothelium by aspirin and dipyridamole

Abstract

An experimental model system has been developed to study the interaction of platelets with a damaged vessel wall, in vivo, without deep surgical intervention. Endothelium of the central ear artery of an anesthetized rabbit is damaged by placing artery forceps on the ear directly over the vessel. Forceps are removed 30 min later and blood flow resumes. After 30 min, blood is washed out with Tyrode's solution and the vessel is perfused with 1% glutaraldehyde solution. Tissue containing the vessel is then removed and further prepared for scanning and transmission electron microscopy. Damage to the endothelium observed by scanning electron microscopy included separation of adjacent endothelial cells (EC); partial destruction and lifting up of some EC, exposing subendothelium; and denudation of larger areas of endothelium. Disc-shaped platelets were seen clinging to some damaged endothelial cells. Platelets adhered, formed pseudopods, and spread over the surface of some areas of exposed subendothelium. The extent of platelet adhesion to exposed subendothelium was estimated by eight "blind" evaluators and the average taken. Aspirin (8 mg/kg, ip) significantly inhibited adhesion (P less than 0.05) when compared to controls. No other agent tested gave significant inhibition after a single treatment. Dipyridamole (1.5 mg/kg, ip) given five times on 3 successive days, inhibited adhesion significantly (P less than 0.001). Heparin (800 U/kg, iv) or dipyridamole (0.7 mg/kg, ip) enhanced the inhibitory effect of aspirin (8 mg/kg, ip), with either combined treatment giving P less than 0.001.