INCREASE IN SKIN-FLAP SURVIVAL BY THE VASOACTIVE DRUG BUFLOMEDIL

The effect of buflomedil to protect skin tissue from ischemia and necrosis was studied in random cutaneous flaps. Measurements were performed by intravital microscopy on the microcirculatory level of capillary perfusion in a flap model in the hairless mouse. In 30 hairless mice, single-pedicle flaps measuring 6 x 16 mm were raised perpendicular to the spine of the animal. This flap develops a reliable amount of necrosis at its distal edge over a period of 7 days. A group of 10 mice received intravenous injections of buflomedil in doses of 3 mg/kg per day diluted in 0.1 ml normal saline beginning 4 hours before flap elevation and for 6 consecutive days postoperatively. In addition, 10 further animals received the same treatment except that it was started 5 minutes after flap elevation. In 10 mice serving as controls, normal saline in equal volumes as in the experimental groups was applied. By means of intravital microscopy, functional vessel density (FVD) was determined in 2.5-mm increments from the flap's base to its distal edge at 1, 6, and 24 hours after elevation. Skin-flap survival was quantified by measuring the necrotic area on day 7 by means of digital planimetry. Functional vessel density was preserved in the distal flap of animals pretreated with buflomedil, revealing a higher functional vessel density at 10.0 mm (p < 0.01), 12.5 mm (p < 0.05), and 15.0 mm (p < 0.001), from the flap's base as compared with controls. In the animals treated after raising the flap, functional vessel density was preserved at 12.5 mm (p < 0.05) and 15.0 mm (p < 0.01) from the flap's base as compared with controls. At 10.0 mm, functional vessel density was higher (p < 0.01) in pretreated animals as compared with animals treated after surgery. On day 7 after flap elevation, the amount of necrotic tissue was reduced from 28 percent in controls to 0 percent (p < 0.001) in pretreated animals and to 4 percent (p < 0.001) when treatment was started after flap elevation, without statistical differences between the two treatment groups (preoperative and postoperative). Buflomedil was found to protect and improve the microvascular perfusion and tissue survival in random-pattern skin flaps, which are known by experience to be at high risk to develop necrosis.