The effect of endothelin-1 levels on skin flap survival

N. Tane, H. Inoue, M. Aihara, H. Ohshima, K. Matsuzaki, H. Ishida

Research output: Contribution to journalArticlepeer-review


A vasospasm in the microvascular circulation can be a cause of flap necrosis, and to maintain flap circulation the vascular endothelium plays an important role in regulating the vascular tone by producing vasodilating and vasoconstricting factors. In this latter regard, endothelin-1 (ET-1), a 21 amino acid polypeptide of the vascular endothelium, is reported to be one of the most potent vasoconstrictors. Therefore, to elucidate the causes for flap necrosis, the authors have evaluated the effect of ET-1 on flap survival by investigating time course changes in the ET-1 levels in skin flap of the rat back. The level and distribution of ET-1 in the flap tissue were initially assessed, and it was found that during the first 3 hours after flap elevation, the ET-1 levels in the flaps were significantly lower than their baseline ET-1 values. However, from the 6 hours onwards, the ET-1 level began to increase, reaching at 24 hours a level that was 180% of the 0 hour level in terms of the absolute amount (about 140% of the content per unit weight). Then, the ET-1 level peaked at 24 hours and maintained this level thereafter. The authors feel that the low ET-1 levels observed during the first 3 hours are probably attributable to a temporary ET-1 release from the flap tissue or to a temporarily reduced ET-1 production, caused by the stress associated with flap elevation. From 6 hours onwards, however, the ET-1 levels of the flap base significantly increased, whereas the ET-1 levels at the flap periphery presented no remarkable changes. These results suggest that ET-1, especially ET-1 produced in the flap base, exerts a major effects on the flap microcirculation. On investigating the sites of ET-1 production, it was found that the ET-1 level at 0 hour did not differ among the 3 segments of the flap. Over the subsequent 6 hours, however, the ET-1 levels in the flap periphery increased significantly and then returned to a level approximating the 0 hour level. At the flap base, the ET-1 levels initially showed no decrease but then increased significantly from the 6 hours onwards. These results suggest that ET-1 exerts a major effect on the microcirculation, and that the ET-1 produced in the flap base regulates the blood flow to the distal region of the flap, which is important for flap survival. Vasoconstriction induced by ET-1 is characterized by sausage-like vasospasms that hemodynamically promote a turbulent flow at the exit, thereby enhancing platelet aggregation in association with changes in the production of bioactive substances. The authors are now investigating other factors that may affect flap survival by analyzing changes in the flap blood flow and the levels of other vasoactive substances in the flap, to determine whether some chemical delay may be the cause of skin flap necrosis.

Original languageEnglish
Pages (from-to)541-547
Number of pages7
JournalJapanese Journal of Plastic and Reconstructive Surgery
Issue number5
Publication statusPublished - 1995 Jan 1

ASJC Scopus subject areas

  • Surgery


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