Prevention of Anastomotic Thrombosis by Botulinum Toxin A in an Animal Model
Mark W. Clemens, MD1, James Higgins, MD2, E.F. Shaw Wilgis, MD3.
1Georgetown University Hospital, Washington, DC, USA, 2The Curtis National hand Center, Union Memorial Hospital, Baltimore, MD, USA, 3The Curtis National Hand Center, Union Memorial Hospital, Baltimore, MD, USA.
BACKGROUND: Free tissue transfer is used widely for the reconstruction of complex defects and disorders throughout the body. A free flap’s success is dependent upon a variety of factors, however the most common cause for failure of the free flap remains vascular thrombosis. Factors contributing to a difficult anastomosis include vasospasm, trauma to the zone of injury, radiation, scar, and infection. Many of these mechanisms are sympathetically mediated. Currently, there exists no animal model for anastomotic vasospasm. Botulinum toxin type A is used extensively in the cosmetic industry for selective muscle paralysis. Recent literature has demonstrated the successful utility of botulinum toxin A for the treatment of vasospasm in Raynaud’s phenomenon.
METHODS: A blinded prospective vasospasm assay was designed to determine the ability of botulinum toxin A to prevent anastomotic thrombosis. Ten Sprague Daley rats were pretreated with a neuromuscular blocking agent, botulinum toxin A subcutaneously to a randomly determined femoral vessels. Animals acted as their own controls, receiving saline to the contralateral limb. Five days postoperatively, the animals underwent femoral vessel measurements to determine the effect of neuromuscular blockade on vessel diameter. Vessels were then divided and re-anastomosed by a single surgeon. Time of suturing and ease of anastomosis were recorded outcomes. Following suturing, animals were subjected to a systemic treatment with a peripheral vasoconstrictor, phenylephrine, and a lower extremity thermic challenge in an ice bath. (16ºC) Vessel patency was recorded at Time 0 (before thermic challenge) and 1 hour after. Comparisons were by paired t test or chi-square test as appropriate.
RESULTS: Vessel diameter was consistently larger in all neuromuscularly blocked animals. The botulinum toxin treated arterial average of 0.68 +/- 0.2 mm (mean +/- SEM) was significantly larger (p = 0.001) than the matched control saline arterial average of 0.53 +/- 0.02 mm. The botulinum toxin treated venous average of 0.95 +/- 0.05 mm was significantly larger ( p = 0.006) than the matched control saline venous average of 0.73 +/- 0.05 mm. Ease of anastomosis and time of suturing were significantly less in the pretreated botulinum toxin group. Vasospastic challenge resulted in 89% of animals thrombosing either an artery, vein, or both. Patency was maintained in 100% of botulinum toxin treated vessels and 44% of saline treated vessels at 1 hour (p<0.001)
CONCLUSIONS: A viable assay to evaluate vasospasm and vessel thrombosis was achieved by treating animals with a systemic peripheral vasoconstrictor and thermic challenge. Significant enlargement of botulinum toxin A treated vessels was observed which resulted in decreased operative time. Botulinum toxin A was successful in preventing thrombosis within this model. The ability for botulinum toxin to decrease vasospasm and thrombosis may have applications for improving free flap survival in select patients.