The Effect of Topical Tacrolimus on Pedicled Flap Survival

Abstract

Purpose Skin necrosis is a known postoperative complication of mastectomies. The pathophysiology of tissue necrosis involves lymphatic congestion, followed by venous congestion and ultimately arterial insufficiency. Recent mouse model studies have shown topical tacrolimus to increase growth of lymphatic collateral vessels and decrease lymphedema, potentially obviating the cycle of necrosis and increasing skin survival. The purpose of this study was to investigate the effect of topical tacrolimus on skin flap necrosis in a rat model. Methods A cranially based dorsal skin flap measuring 3 × 10 cm was raised and reinset on 22 Sprague-Dawley rats. They were then randomized to either the control (topical petroleum jelly) or the treatment (topical 0.1% tacrolimus) arm. In addition, 0.2 g of either ointment was spread over the flap and then covered with an occlusive dressing. Dressings were changed daily with reapplication of both the topical ointment and occlusive dressing. The rats were sacrificed 7 days postoperatively; areas of viable tissue, reversible ischemia, and full thickness necrosis were measured with Fiji software, and comparative analysis was performed with GraphPad statistical software. Results The average area of the dorsal flaps in the control and tacrolimus groups was 22.5 and 23.9 cm2, respectively. In the control cohort, the average viable area was 42.4%, the average reversible ischemia area was 43.6%, and the average necrotic area was 13.9%. In the tacrolimus cohort, the average viable area was 31.5%, the average reversible ischemia area was 59.3%, and the average necrotic area was 9.2%. Total necrotic area was significantly lower in rats receiving topical tacrolimus as compared with controls (P = 0.015). Furthermore, the ratios of necrotic to reversible ischemia and necrotic to viable tissue were significantly lower in the tacrolimus group as compared with controls (P = 0.003, P = 0.015). There was one incidence of wound dehiscence secondary to rodent self-removal of dressings and suture that required reoperation and reinset. Conclusions Topical tacrolimus was associated with significantly less full thickness necrosis as compared with topical.

The Effect of Topical Tacrolimus on Pedicled Flap Survival

“…An abridged version of the techniques used in our animal model is described hereinafter; further detail may be gleaned from our original article 6 …”

“…Our previous rodent study demonstrated significantly decreased full-thickness necrosis in pedicled dorsal skin flaps with topical tacrolimus as compared with petroleum jelly, with an average of 33.8% less necrotic area. 6 The purpose of this study was to investigate the vascular and histological differences between these 2 groups to identify the etiology of our previous research findings.…”

The Effect of Presurgical and Postsurgical Topical Tacrolimus on Pedicled Flap Survival in Rats

“…To our knowledge, our study is the first to evaluate the prophylactic use of topical tacrolimus to decrease ischemia and skin necrosis after injury in the rat model. Our group has previously shown tacrolimus application after injury significantly decreased the total necrotic area compared with controls 3 . Upon further histological analysis, we also demonstrated topical tacrolimus increased arterial, venous, and lymphatic growth in areas that were most susceptible for ischemic damage 6 …”

“…Our group has previously shown tacrolimus application after injury significantly decreased the total necrotic area compared with controls. 3 Upon further histological analysis, we also demonstrated topical tacrolimus increased arterial, venous, and lymphatic growth in areas that were most susceptible for ischemic damage. 6 Although the regulation of angiogenic and lymphangiogenic factors involved with wound healing is complex, the pharmacokinetic effects of topical tacrolimus doses most likely are associated with lymphangiogenic mechanisms involved with T-cell inflammatory responses.…”

“…2 Our previous rodent studies demonstrated significantly decreased full-thickness necrosis in tacrolimus-treated pedicled dorsal skin flaps with an average of 33.8% less necrotic area as compared with controls and showed that there were increases in all types of vasculature (arterial, venous, and lymphatic) in flaps treated with tacrolimus. 3 The purpose of this study was to investigate whether pretreatment with tacrolimus would be beneficial in further preventing tissue necrosis.…”