title: Failure of certain antiplatelet drugs to affect myointimal thickening following arterial endothelial injury in the rat.
abstract: The effect of aspirin, reserpine, and flurbiprofen on in vivo platelet function and intimal smooth muscle cell hyperplasia in rat carotid arteries subjected to endothelial injury was investigated and related to the effect of these drugs on in vitro platelet aggregation. Endothelial injury was achieved by infusing air briefly into a segment of right common carotid artery. Beginning before or after surgery, experimental animals were given sufficient drug to suppress platelet aggregation in vitro in response to collagen, adenosine diphosphate, or thrombin. The carotid arteries were fixed by perfusion at 5 and 14 days after injury and examined by light, scanning electron, and transmission electron microscopy for platelet activity and intimal smooth muscle cell proliferation in the denuded segment. Platelets in platelet-rich plasma from control animals aggregated in response to collagen, adenosine diphosphate, and thrombin; platelets from aspirin-, flurbiprofen- and reserpine-treated rats showed markedly diminished aggregation in response to collagen and normal or slightly diminished aggregation in response to ADP and thrombin. At 5 days, platelets from control animals formed a dense layer in the denuded segment: at 14 days, marked intimal thickening due to smooth muscle cell hyperplasia was observed. In experimental animals, the platelets were morphologically identical with controls and covered the denuded segment; serotonin granules were missing in platelets of reserpine-treated rats. Intimal thickening at 14 days was the same as controls. We conclude that in the rat no correlation may be made between the effect of aspirin, reserpine, and flurbiprofen on in vitro platelet aggregation and the effect of these drugs on the function of platelets on an arterial wall denuded of endothelium, as judged by morphology; furthermore, even when these drugs are used in sufficient dose to inhibit in vitro aggregation of platelets, myointimal thickening is not inhibited.
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000388:Air; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D003018:Clot Retraction; D003094:Collagen / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D005480:Flurbiprofen / Q000494:pharmacology*; D006965:Hyperplasia; D008297:Male; D008643:Mesentery; D008954:Models, Biological; D009130:Muscle, Smooth / Q000473:pathology; D010974:Platelet Aggregation / Q000187:drug effects*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D012038:Regeneration; D012110:Reserpine / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D011422:Propionates; D005480:Flurbiprofen; D000244:Adenosine Diphosphate; D012110:Reserpine; D003094:Collagen; D013917:Thrombin; D001241:Aspirin