{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T17:37:23Z","timestamp":1784569043124,"version":"3.55.0"},"reference-count":0,"publisher":"Canadian Science Publishing","issue":"1","license":[{"start":{"date-parts":[[1994,1,1]],"date-time":"1994-01-01T00:00:00Z","timestamp":757382400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[1994,1,1]]},"abstract":"<jats:p> There is clinical and experimental evidence to indicate that cigarette smoking may increase the risk of skin ischemic necrosis in flap surgery but the pathogenic mechanism remains unclear. The objectives of this project were to investigate the potential deleterious effects and mechanism of action of nicotine, a major by-product of cigarette smoking, in skin flap surgery in the pig. It was observed that 4\u20135 weeks of intramuscular nicotine injections (4\u2002mg\/kg; twice daily) significantly (p\u2002&lt;\u20020.05) decreased the skin flap capillary blood flow and the length and area of skin flap viability in the pig. This nicotine treatment also induced a 1.6-fold increase in skin flap tissue content of norepinephrine compared with the saline-treated control. The estimated mean wet skin tissue content of norepinephrine (5\u2002\u00d7\u200210<jats:sup>\u22127<\/jats:sup>\u2002M) was much higher than the circulating level of norepinephrine (1.8\u2002\u00d7\u200210<jats:sup>\u22129<\/jats:sup>\u2002M) in nicotine-treated pigs. This level of norepinephrine (5\u2002\u00d710<jats:sup>\u22127<\/jats:sup>\u2002M) was seen to induce a significant vasoconstrictor effect (75% increase over basal perfusion pressure) in isolated perfused pig skin flaps. It was also observed that the vasoconstrictor effect of norepinephrine was significantly (p\u2002&lt;\u20020.05) enhanced in the presence of 10<jats:sup>\u22124<\/jats:sup>\u2002M N<jats:sup>\u03c9<\/jats:sup>-monomethyl-L-arginine or N<jats:sup>G<\/jats:sup>-nitro-L-arginine, an endothelium-derived relaxing factor \u2013 nitric oxide (EDRF\/NO) synthesis inhibitor. This vasoconstrictor effect was further enhanced in the presence of N<jats:sup>G<\/jats:sup>-nitro-L-arginine and 10<jats:sup>\u22125<\/jats:sup>\u2002M indomethacin, a cyclooxygenase inhibitor. Taken together, these observations indicate that 4\u20135 weeks of nicotine treatment significantly reduced the skin capillary blood flow and viability in skin flap surgery in the pig and this deleterious effect was likely to be mediated, at least in part, by locally released norepinephrine induced by nicotine treatment. Furthermore, norepinephrine also induced skin flap local release of EDRF\/NO and a vasodilating prostanoid that in turn attenuated norepinephrine's vasoconstrictor effect in the skin vasculature. We speculate that skin vasculature with compromised endothelial cell function as a result of trauma or disease is more susceptible to the vasoconstrictor effect of norepinephrine released by nicotine.Key words: chronic nicotine, norepinephrine, skin vasoconstriction, flap surgery. <\/jats:p>","DOI":"10.1139\/y94-006","type":"journal-article","created":{"date-parts":[[2011,4,23]],"date-time":"2011-04-23T17:04:23Z","timestamp":1303578263000},"page":"30-38","source":"Crossref","is-referenced-by-count":30,"title":["Evidence for nicotine-induced skin flap ischemic necrosis in the pig"],"prefix":"10.1139","volume":"72","author":[{"given":"Christopher R.","family":"Forrest","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cho Y.","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","container-title":["Canadian Journal of Physiology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nrcresearchpress.com\/doi\/pdf\/10.1139\/y94-006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,1,5]],"date-time":"2020-01-05T10:21:39Z","timestamp":1578219699000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.nrcresearchpress.com\/doi\/10.1139\/y94-006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,1,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1994,1,1]]}},"alternative-id":["10.1139\/y94-006"],"URL":"https:\/\/doi.org\/10.1139\/y94-006","relation":{},"ISSN":["0008-4212","1205-7541"],"issn-type":[{"value":"0008-4212","type":"print"},{"value":"1205-7541","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,1,1]]}}}