Improved perfusion after subcritical ischemia in muscle flaps treated withvascular endothelial growth factor

Vascular endothelial growth factor (VEGF), a potent endothelial mitogen, is secreted in ischemic tissue and plays a pivotal role in angiogenesis. We s tudied whether VEGF administered to a rat muscle flap at the time of ischem ia induction would increase microcirculatory flow to the flap. The cremaste r muscle flap was isolated on its neurovascular pedicle. Ischemia was induc ed by clamping the vascular pedicle, and 0.2 ml of either VEGF (0.1 mug) or vehicle (phosphate-buffered saline) was immediately infused into the muscl e. After 4 or 6 hours, the clamps were released, and the cremaster was plac ed in a pocket in the medial thigh for 24 hours. The muscle was then dissec ted, and microcirculatory measurements were made under intravital microscop y. Six animals were used in each of the four groups. All flaps exposed to 6 hours of ischemia, the duration considered to be cri tical ischemia, had no significant microcirculatory flow, regardless of tre atment with VEGF. In the 4-hour ischemia group, or subcritical ischemia gro up, red blood cell velocity in arterioles was 14 mm/sec in muscles treated with VEGF and 9 mm/sec in controls (p = 0.02), and capillary flow was 17 pe r high-power field in muscles treated with VEGF versus 2 per high-power fie ld in controls (p = 0.0005). Thus, VEGF did not alter microcirculatory flow in a muscle flap exposed to critical ischemia, but it did enhance flow to a flap exposed to subcritical ischemia.