To evaluate the pathogenesis of lipid peroxidation in skin-flap
necrosis and to select a novel herbal
antioxidant to suppress lipid peroxidation and salvage the flaps, in vitro and in vivo experiments were instituted. In vitro studies revealed (1) the potentiality of the cutaneous microsomal system (vesicular fragment of endoplasmic reticulum) to generate oxyradicals by FeCl3 (oxidative agent), since
NADPH-dependent lipid peroxidation was elevated time-dependently, (2) suppression of microsomal lipid peroxidation by herbal
antioxidants (dose- and time-dependently), further supporting the theory of oxyradical-induced lipid peroxidation in the skin, and (3) that
ellagic acid showed the strongest response, with
curcumin,
chlorogenic acid, and
alpha-tocopherol (
tocopherol) being moderate, and
ferulic acid and
gallic acid remaining weakest. Thus
ellagic acid,
curcumin,
chlorogenic acid, and
tocopherol at doses of 10, 60, 80 and 100 microM (twice I50, the dose which could inhibit lipid peroxidation by 50 percent) were chosen for in vivo assessments, respectively. In vivo studies were performed using rat back skin random flaps (70 x 15 mm and based anteriorly) and circular
island flaps (20 mm in diameter and raised on superficial epigastric vessels). Control flaps were painted with a Tris-
ethanol solution, and test flaps were painted with either
ellagic acid,
curcumin,
chlorogenic acid, or
tocopherol (above-mentioned doses per 250 microliters of Tris-
ethanol per 300 mm2 of flap surface 1 hour before the operation and once a day for 3 postoperative days). Doses, frequency, and period of
drug application were based on in vitro and in vivo pilot experiments. The results were as follows: (1) a direct and time-dependent relation was noticed between
lipid peroxide levels and the rate of
necrosis in both types of flap; (2) time-dependent elevation of
lipid peroxide levels of skin, subcutaneous fat, and exudate of
island flaps during
ischemia and those of skin and subdermal fat after reperfusion indicated pre- and post-reflow states of lipid peroxidation rather than the original conception of merely reperfusion state; and (3) in good agreement with the results of in vitro experiments,
ellagic acid exerted the strongest effect to suppress
lipid peroxide levels of skin and to augment the viability of random flaps more than that of
island flaps.(ABSTRACT TRUNCATED AT 400 WORDS)