Augmentation of rat skin flap viability by relaxin-expressing adenovirus

Relaxin (RLX) has multiple vascular actions, including vasodilation and angiogenesis, which occur via induction of vascular endothelial growth factor (VEGF) expression. We generated a RLX-expressing (dE1-RGD/lacZ/RLX) adenovirus and investigated whether it enhances skin flap survival. Thirty Sprague-Dawley rats were divided into three groups: RLX-expressing adenovirus group, control virus group, and phosphate-buffered saline (PBS) group. Two days before surgery and immediately after flap elevation, the caudally based flap that was 3 × 9 cm in size was subdermally injected with the dE1-RGD/lacZ/RLX virus (10⁷ PFU), dE1-RGD/lacZ virus (10⁷ PFU), or PBS. The surviving area of the flap and the amount of blood flow were measured. On postoperative day 10, CD31-positive vessels and VEGF protein expression were examined. We observed a significant increase in the survival area of the flap in the RLX group. Doppler measurement also showed significantly increased blood flow immediately after the operation and on postoperative days 7 and 10. CD31-positive vessels and VEGF protein expression were significantly greater in the RLX group. Thus, administration of RLX-expressing adenovirus into elevated skin flaps increased VEGF expression, the number of capillaries, and blood flow to the flap, thereby improving skin flap survival.