Protamine induces vasorelaxation of human internal thoracic artery by endothelial NO-synthase pathway

Background. Protamine is commonly used in cardiac surgery to reverse the an ticoagulant effects of heparin. We investigated the role of different nitri c oxide synthase pathways in the response of the human internal thoracic ar tery to protamine and evaluated whether heparin could prevent this effect. Methods. A tension-recording method was used to obtain baseline measurement s of contractions of human internal thoracic artery rings achieved with nor epinephrine. Isolated internal thoracic artery rings were suspended in two organ chambers. One contained Krebs-Henseleit solution and served as contro l. The other contained a heparin or N omega -Nitro-L-arginine (L-NAM, an in hibitor of both endothelial and inducible nitric oxide synthase) or a speci fic inhibitor of inducible nitric oxide synthase, aminoguanidine. Increasin g doses of protamine were added to both chambers and dose;response curves w ere obtained, Results. Protamine was found to relax contracted internal thoracic arteries 56% +/- 4.7% of baseline measurements in a concentration-dependent manner. When L-NAM was added, protamine caused only a slight decrease of tension. There were no differences in the relaxing effect of protamine in the presen ce of aminoguanidine or heparin; Conclusions. Protamine induces nitric oxide-dependent relaxation of the int ernal thoracic artery by activation of endothelial nitric oxide synthase pa thway. Heparin could not prevent this relaxing effect of protamine. (Ann Th orac Surg 2000;70:2050-3) (C) 2000 by The Society of Thoracic Surgeons.