Effect of botulinum toxin a and nitroglycerin on random skin flap survival in rats

Abstract

Background A suitable pharmacological substitute for the well-established surgical delay technique for random skin flaps to increase viability has been elusive. Objective To evaluate the effects of nitroglycerin and botulinum toxin type A on random flap survival in a rat model. Methods The present controlled experimental study was performed in the four groups of rats. One week after intervention in each group, the flap was raised and kept in situ, and flap necrosis was evaluated through follow-up. Group 1 received intradermal botulinum toxin type A (BTX-A) and topical nitroglycerin 2%; group 2 received BTX-A and topical Vaseline (Unilever, USA); group 3 received topical nitroglycerin and intradermal normal saline; and group 4 received topical Vaseline and intradermal normal saline. Results BTX-A reduced the area of necrosis compared with control (24% versus 56% respectively; P<0.001). Nitroglycerin application was associated with a trend toward improved flap viability (42% versus 56%; P=0.059). The combination of topical nitroglycerin and BTX-A, compared with Vaseline and BTX-A, was associated with decreased flap necrosis (16.1% versus 24%, respectively), although it was not statistically significant (P=0.45). Conclusions BTX-A was effective in reducing distal flap necrosis. The effect of BTX-A was significantly more pronounced than nitroglycerin ointment.

The effect of nitroglycerin in the zone of stasis in a rat burn model

“…In an experimental study, botulinum toxin A and nitroglycerin increased flap viability on random skin flaps. [25] Topical nitroglycerin was also used in the management of tissue ischemia in mastectomy skin flaps, and as in our study, improvement in perfusion was shown but differently by angiography. [26] We aimed to limit the progression of necrosis and to salvage the zone of stasis.…”

The Use of Botulinum Toxin in Flap Surgery: A Review of the Literature

“…Fourteen studies had a control group, while 3 had an internal control. Four articles referred to random myocutaneous flaps, 9-12 8 to cutaneous flaps (5 random pattern 13-17 and 3 axial 18-20 ), 1 to axial muscle flap, 21 1 to axial fat-cutaneous flap, 22 and 3 to free flaps or vascular anastomosis. 23-25 Fifteen studies used BTX A, 9-17,19,23,25 1 used BoNT-A and BoNT-B, 18 and 1 used only BoNT-B.…”

“…Five studies used the intradermal technique with random flap. 12,[14][15][16][17] Kim et al 13 compared the intradermal and subdermal injection techniques with noninjected control group. In their pilot study, injecting deeper than the subdermal layer, namely, within the subcutaneous layer, worsened muscle atrophy with an increased rat fatality rate and no outcome improvement in flap survival.…”

Role of botulinum neurotoxin–A in cerebral revascularization graft vasospasm prevention: current state of knowledge

“…1,6-8, 10, 22, 32, 36, 39, 40, 49, 50, 54, 57,62 In these studies, a rat model was most commonly used (n = 14/15) and there was significant variability in BTX dose (0.1-20 IU), application method (subdermal, intradermal, subcutaneous, intramuscular or perivascular injection, direct application to the vessels, or tissue bath), treated flaps (random cutaneous, abdominal or dorsal cutaneous, transverse rectus abdominis myocutaneous, cremaster, spinotrapezius, or gastrocnemius muscular), and evaluation time points (5 minutes to 21 days). Better flap survival rates, 10,22,32,36,39,50,54,57 increased angiogenesis and angiogenic marker expression, 36,39,40,49,50,54 improved blood flow, 54,57 vasodilation, 8,39,50,62 and reduced inflammation and inflammatory marker expression 1,6 were observed in the BTX treatment groups as compared to controls. Interestingly, BTX-A also improved random cutaneous flap survival in rats after short-and long-term tobacco exposure, demonstrating its potential efficacy for the prevention of reconstructive and revascularization surgery complications in smokers.…”