title: Pharmacologic enhancement of rat skin flap survival with topical oleic acid.
abstract: This study was instituted to investigate in a rat model the effect of topical coadministration of the penetration enhancer oleic acid (10% by volume) and RIMSO-50 (medical grade dimethyl sulfoxide, 50% by volume) on rat skin flap survival. A rectangular abdominal skin flap (2.5 x 3 cm) was surgically elevated over the left abdomen in 40 nude rats. The vein of the flap's neurovascular pedicle was occluded by placement of a microvascular clip, and the flap was resutured with 4-0 Prolene to its adjacent skin. At the end of 8 hours, the distal edge of the flap was reincised to gain access to the clips and the clips were removed. After resuturing of the flap's distal edge to its adjacent skin, the 40 flaps were randomly divided into four groups. Group 1 (control) flaps were treated with 5 g of saline, group 2 (dimethyl sulfoxide) flaps were treated with 2.7 g of dimethyl sulfoxide (50% by volume), group 3 flaps (oleic acid) were topically treated with 0.45 g of oleic acid (10% by volume), and group 4 (dimethyl sulfoxide plus oleic acid) flaps were treated with a mixture of 0.45 g of oleic acid (10% by volume) and 2.7 g of dimethyl sulfoxide (50% by volume) diluted in saline. Each flap was topically treated with 5 ml of drug-soaked gauze for 1 hour immediately after clip removal to attenuate reperfusion injury. Thereafter, drug was applied topically once daily for 4 more days. Digital photographs of each flap were then taken on day 6 and the flaps were then harvested. The percentage of skin survival in each flap was determined by computerized morphometry and planimetry. The mean surviving area of group 3 (oleic acid-treated flaps) was 23.60 +/- 4.19 percent and was statistically higher than that in group 1 (control, saline-treated flaps) at 7.20 +/- 2.56 percent. The mean surviving area of group 2 (dimethyl sulfoxide-treated flaps) at 18.00 +/- 5.23 percent and group 4 (oleic acid- and dimethyl sulfoxide-treated flaps) at 9.90 +/- 3.44 percent did not achieve statistically higher mean surviving areas than controls. A topical solution of oleic acid (10% by volume) caused a statistically significant increase in the survival of rat abdominal skin flaps relative to controls. Dimethyl sulfoxide and the two experimental drugs together did not increase the percentage of flap survival when given as a single 5-ml dose released from a surgical sponge at reperfusion for 1 hour and then daily for a total of 5 days. The reasons for the lack of response are unknown but may have included the technical difficulty of delivering an adequate dose of dimethyl sulfoxide topically and immiscibility between dimethyl sulfoxide and oleic acid. Further studies may be warranted.
authors.affiliation: Aesthetic and Plastic Surgery Institute, University of California, Irvine, USA.
authors.forename: Oscar K
authors.initials: OK
authors.lastname: Hsu
authors.forename: Essam
authors.initials: E
authors.lastname: Gabr
authors.forename: Earl
authors.initials: E
authors.lastname: Steward
authors.forename: Heidi
authors.initials: H
authors.lastname: Chen
authors.forename: Mark R
authors.initials: MR
authors.lastname: Kobayashi
authors.forename: Jay W
authors.initials: JW
authors.lastname: Calvert
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sundine
authors.forename: Taline
authors.initials: T
authors.lastname: Kotchounian
authors.forename: Sanjay
authors.initials: S
authors.lastname: Dhar
authors.forename: Gregory R D
authors.initials: GR
authors.lastname: Evans
mesh_terms: D000005:Abdomen; D000287:Administration, Topical; D000818:Animals; D062109:Dermatologic Surgical Procedures; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage; D016166:Free Radical Scavengers / Q000008:administration & dosage; D006085:Graft Survival / Q000187:drug effects*; D008297:Male; D019301:Oleic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D013524:Surgical Flaps
chemical_list: D016166:Free Radical Scavengers; D019301:Oleic Acid; D004121:Dimethyl Sulfoxide