Angiogenesis and reinnervation in skin flaps: the effects of ischaemia examined in an animal model.

In clinical flap transplantation, ischaemia may alter reinnervation patterns either directly or by affecting angiogenesis. This study presents the effects of ischaemia on innervation in totally denervated, transiently (30 minutes) or prolongedly ischaemic skin flaps studied immunohistochemically with antisera to PGP 9.5, CGRP and VWF. Following transient ischaemia, an increase in PGP-immunoreactive (PGP-IR) and CGRP-IR nerve fibres in distant skin by day 12 was followed by increased innervation in immediately adjacent skin. The latter increase was maintained up to 24 days which allowed near normal innervation at the suture margin and in adjacent flap tissue, 0.5 cm from the margin. There was concomitant reinnervation from the pedicle by day 24. In prolongedly ischaemic flaps, an earlier and more prolonged increase in innervation was seen in the entire surrounding skin, with innervation around the suture line at 24 days resembling that in the transiently ischaemic flaps despite initial complete nerve fibre depletion in this area. Hypertrophic nerve fibre clusters were seen in fibrotic areas overlying the pedicle. Vascular changes were similar in both groups with vascularization preceding reinnervation. There were no significant differences in reinnervation between the transiently and prolongedly ischaemic flaps at 24 days, despite considerable initial variations. Ischaemia, CGRP, mediators of chronic inflammation and epidermal factors appeared to stimulate angiogenesis and reinnervation.