Angiotensin II improves random-flap viability in a rat model

Angiotensin II (AII) is a naturally occurring peptide that has been shown t o be angiogenic, cause the proliferation of several primary cell types (inc luding endothelial cells), accelerate the repair of dermal injuries, and in crease production of growth factors and extracellular matrix. The effect of a single administration of All on the viability and vascularity of a rando m flap was assessed in a rat model. In the control model, the viability of the distal portion of the flap was reduced consistently by postoperative da y 8. Initially, ARI was administered in an aqueous vehicle (phosphate-buffe red saline [PBS]) and a viscous vehicle (10% carboxymethyl cellulose [CMC]) . Administration of 1 mg per milliliter All in PBS did not affect the viabi lity of random flaps (1.2 x 7 cm) in this animal model. However, a single a dministration of a higher dose of All in PBS (10 mg per milliliter) or 1 mg per milliliter All in the CMC vehicle resulted in 67% of the grafts being fully viable at postsurgical day 12, in contrast to vehicle-treated control flaps, none of which were fully viable at day 12. Furthermore, the portion of the flap that was viable was increased significantly (p less than or eq ual to 0.05). Subsequently, a study was conducted to assess the dose-respon se curve for AII in a CMC vehicle in this rat model, As the dose of All was reduced, the percentage of animals with fully viable flaps and the percent age of the flap that was viable decreased correspondingly. Administration o f 0.03 mg per milliliter All and greater increased significantly (p less th an or equal to 0.05) the viability of the flaps. In conclusion, All appears to be highly efficacious in increasing the percentage of distal flap surfa ce area survival when administered as a single topical dose to the wound be d.