Prothrombotic cytotoxicity of cyanoacrylate tissue adhesive.
Alkyl-2-cyanoacrylates exhibit properties suggestive of their use as surgical adhesives; however, their cytotoxic and proinflammatory properties have prevented their widespread application. The question of whether cyanoacrylate cytotoxicity may be due to eicosanoid production was investigated. Endothelial cells from rats were exposed to increased concentrations of isobutyl-2-cyanoacrylate. The products from this exposure promoted enhanced, concentration-dependent thromboxane biosynthesis as detected by platelet aggregation. When platelets were pretreated with 1-carboxyheptylimidazole (2.0 mM), an inhibitor of thromboxane biosynthesis, up to 80% less aggregation was observed. Such aggregation was inhibited using 1-carboxyheptylimidazole in a dose-dependent manner. Treatment of endothelial cells with isobutyl-2-cyanoacrylate and 1-carboxyheptylimidazole did not significantly alter the amount of platelet aggregation. A soluble metabolite of isobutyl-2-cyanoacrylate appeared to activate platelet aggregation. The cytotoxicity associated with the surgical use of alkyl-2-cyanoacrylates may be mediated by enhanced local thromboxane production.
Papatheofanis
F J
FJ
Department of Orthopedic Surgery, University of Illinois, Chicago 60680.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002015:Bucrylate / Q000494:pharmacology / Q000633:toxicity*; D002478:Cells, Cultured; D003487:Cyanoacrylates / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000097:blood*; D014014:Tissue Adhesives
D003487:Cyanoacrylates; D007093:Imidazoles; D014014:Tissue Adhesives; D002015:Bucrylate; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; C024335:1-(7-carboxyhexyl)imidazole; D007213:Indomethacin