The Effect of Topical Tacrolimus on Pedicled Flap Vascularity: A Histological Analysis
Y-vu R. Van1, Gal Wald2, William Towne1, David Otterburn, MD3.
1New York Presbyterian, NY, NY, USA, 2Weill Cornell Medical College, NY, NY, USA, 3New York Presbyterian, Weill Cornell Medical College, NY, NY, USA.
INTRODUCTIONOur previous rodent study demonstrated significantly decreased full thickness necrosis in pedicled dorsal skin flaps with topical tacrolimus as compared to petroleum jelly. The pathophysiology of tissue necrosis involves lymphatic congestion, followed by venous congestion and ultimately arterial insufficiency. Topical tacrolimus has been shown to increase growth of lymphatic collateral vessels and decrease lymphedema, potentially obviating one contributor to necrosis. The purpose of this study was to investigate the vascular and histological differences between these two groups to identify the etiology of our research findings.
METHODSA cranially based dorsal skin flap measuring 3 x 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 to receive 0.2g of ointment daily to the skin flaps. The rats were sacrificed 7 days postoperatively. Two blinded reviewers marked the total skin flap area as well as areas of viable tissue, reversible ischemia, and necrotic tissue. Full-thickness punch biopsies of each area were taken from 2 randomly chosen animals in each group. Paraffin embedded tissue was sectioned to generate hematoxylin and eosin stained slides. Representative images of each area of the flap were taken under 40X magnification using light microscopy. Arteries, veins and lymphatics in the dermal layer were quantified under blinded conditions by a trained pathologist and calculated per cross sectional area using Fiji software.
RESULTSThe average area of the dorsal flaps in the control and tacrolimus groups was 22.5 and 23.9 cm2, respectively. Total necrotic area was significantly lower in rats receiving topical tacrolimus as compared with controls (P = 0.015). In the control cohort, average total number of vessels was 12.5 in the area of viable tissue, 6 in the area of reversible ischemia, and 0 in the areas of necrosis. In the tacrolimus cohort, average total number of vessels increased was 20 in the area of viable tissue, 11.5 in the area of reversible ischemia, and 5.4 in the areas of necrosis.
CONCLUSIONOn a histological level, topical tacrolimus is correlated with increased vascular growth in areas most susceptible for ischemic damage as compared with topical control. Future work is needed to investigate vascular biomarkers and increase the power of our study.
Back to 2020 Abstracts