An experimental study of the effect of pre-operative administration of cilostazol on random skin flap survival in rats: double blinded randomized controlled trial

Abstract

BackgroundInsufficient arterial blood flow is the one cause of flap necrosis. Cilostazol is an inhibitor of phosphodiesterase III and increases cyclic AMP level in vascular smooth muscle cell causing vasodilation. Therefore, effect of cilostazol is expected to improve the viability of the flap.MethodsDouble blinded randomized controlled trial was conducted. The study was to compare the survival of dorsal rat flaps between preoperative cilostazol supplemented diet and regular diet. The flap survival area was measured using PixArea Image software on post operative day 1,3,5 and 7. Fluorescein injection was performed to evaluate the exactly area of flap survival on postoperative day 7 and morphology of arterioles and venules were examined by histopathologic examination.ResultsA statistical significance was found in the percentage of area of flap survival between cilostazol supplemented diet and control group on postoperative day 3, 5 and 7 (p < 0.05). Fluorescein injection showed the higher area of flap survival in cilostazol group than the control group (p < 0.05). Histopathologic examination showed dilation of vessels in the cilostazol group.ConclusionPreoperative cilostazol in rats can enhance skin flap survival.Electronic supplementary materialThe online version of this article (doi:10.1186/s13022-015-0011-4) contains supplementary material, which is available to authorized users.

Non‐operative adjuncts for the prevention of mastectomy skin flap necrosis: a systematic review and meta‐analysis

“…Cilostazol is a phosphodiesteriase III inhibitor, that acts to both inhibit platelet aggregation while having a profound vasodilatory and anti‐proliferative effect on the vessel wall 45 . It's effect on the microcirculation is well‐documented in animal studies, demonstrating improved survival in both random and axially based flaps survival 46–48 . This efficacy appears consistent in Ghosh's randomized study, the first clinical trial exploring the use of Cilostazol in skin flap necrosis, whereby a statistically significant reduction in both extent and depth of necrosis was discovered 18 .…”

“…45 It's effect on the microcirculation is well-documented in animal studies, demonstrating improved survival in both random and axially based flaps survival. [46][47][48] This efficacy appears consistent in Ghosh's randomized study, the first clinical trial exploring the use of Cilostazol in skin flap necrosis, whereby a statistically significant reduction in both extent and depth of necrosis was discovered. 18 However, it's use in Australia for any indications has not yet been approved by the pharmaceutical benefits scheme, and as such is not applicable in the Australian surgeon's day-to-day practice.…”

Standardization of the Rat Dorsal Random Pattern (McFarlane) Flap Model and Evaluation of the Pharmacological Agents Aiming to Salvage Partial Flap Necrosis

“…Twenty-three studies (31.9%) used cranially based dorsal random pattern flaps, and 49 studies (68.1%) used caudally based dorsal random pattern flaps. Most common flap length  width were 9 cm  3 cm (n = 18), 19,20,22,44,45,[49][50][51][52][53][54][55][56][57][58][59][60][61] followed by 10 cm  3 cm (n = 15), 23,25,30,31,40,42,[62][63][64][65][66][67][68][69][70] 8 cm  2 cm (n = 8), 27,28,33,[71][72][73][74][75] and 6 cm  2 cm (n = 7). 24,[34][35][36]38,76,77 Twenty-one different sized flap models were used (for detailed information about flap models, see Appendix I).…”

Effect of cilostazol in experimental model of degloving injuries in rat limbs

“…Despite the promising findings in cutaneous flaps of rats, it is important to consider that rat skin is different from human skin, mainly because it has a layer of striated muscle located between the dermis and subcutaneous adipose tissue (Panniculus carusus muscle) 23 , which may be responsible for increased blood flow and lower rates of cutaneous necrosis in these mammals. Therefore, the direct comparison of degloving injuries in rats and in humans is difficult 24 . Clinical trials with degloving injuries in human skin may confirm the study's favorable findings.…”