IMPACT OF ISCHEMIA ON TISSUE OXYGENATION AND WOUND-HEALING - INTRAVITAL MICROSCOPIC STUDIES ON THE HAIRLESS MOUSE EAR MODEL

To determine the.effect of ischemia on tissue oxygenation and the healing of experimental wounds, chronic ischemia was induced in the ears of hairless mice by ligating 2 of the 3 main nutritional arteries. Tissue ischemia was verified by measurement of transcutaneous pO2 (tcpO2) Prior to and on days 3, 6, 9, 12 and 15 after vessel ligation. TcpO2 values decreased from 24 to 6 mm Hg at day 2 after ligation, and slowly recovered to 12 mm Hg at day 12 after vessel ligation. In animals treated with the vasoactive drug buflomedil (3 mg/kg BW i.v., starting 2 days after vessel ligation) tcpO2 values were significantly higher on days 6 and 9 when compared to saline-treated control animals. In order to find out whether the enhanced tissue oxygenation resulted in enhancement of healing of wounds, we created circular wounds (diameter = 2.5 mm, depth 0.1 mm) on ischemic ears 2 days after vessel ligation. The wound surface area was measured by means of intravital fluorescence microscopy and digital planimetry at 3-day intervals until the time of wound closure. These experiments were performed on buflomedil-treated and control animals receiving equivalent amounts of saline. The reduction of wound surface area was accelerated and wound closure time was reduced from 15 days in control animals to 12 days in buflomedil-treated animals (p < 0.01). Functional capillary density as well as the microhemodynamic parameters microvessel diameter and red blood cell velocity were not different between buflomedil-treated and control animals.