POSSIBLE CONTRIBUTIONS OF MASTOCYTOSIS, APOPTOSIS, AND HYDROLYSIS IN PATHOPHYSIOLOGY OF RANDOMIZED SKIN FLAPS IN HUMANS AND GUINEA-PIGS

To understand better the pathophysiology of random skin flaps, randomi zed skin flaps of human (3 cases) and guinea pig (53 cases) were inves tigated. Proximal (normal), proximomedial (viable), mediodistal (betwe en viable and necrotic parts), and distal (necrosis) locations of the skin flaps were biopsied. Lipid peroxidase, hydrolytic enzymes of cyto sol (Ca2+-dependent cysteine protease: calpain), and lysosome (acid ph osphatase) of skin were used as markers. Measurements were taken of th e flap blood flow; the numbers of capillaries, postcapillary venules, pericapillary arterioles, leukocytes, and mast cells per unit square o f dermis. Apoptotic cells were identified by specific staining. Flaps were sampled at postoperative weeks 1 and 3 (human) and hours 1 and 6, and days 1 to 7 (guinea pig). The values for normal skin were regarde d as the control. Obstruction (by leukocytes) of venous microvessels, rather than arterial microvessels, was the major cause of temporary hy poxia in the proximomedial location, constant hypoxia (venous stasis) in the mediodistal; location, and ischemia in the distal location. Inc reases in the numbers of mast cells (mastocytosis) and microvessels (a ngiogenesis) were significant only in the viable parts of the flaps. T his phenomenon and the rate of blood flow increased with time in viabl e locations (guinea pig). Epidermal necrosis, dermal fibrosis, and apo ptosis were evident mostly in the mediodistal location. Elevated level s of leukocytes, lipid peroxidase, acid phosphatase, and calpain, comb ined with necrotic changes, were seen mostly in the distal skin locati on. There is a strong possibility that the following factors are invol ved: lipid peroxidation and hydrolysis in necrosis of the distal flap location after ischemia; constant hypoxia in fibrosis and apoptosis in the mediodistal location; and initial or temporary hypoxia in mastocy tosis-induced angiogenesis in the viable location. The results present ed here indicate that guidelines for further investigations include co mbined suppression of leukotaxis, lipid peroxidase, and hydrolysis, or the application of mast cell growth factors in an effort to salvage t he flap maximally.