Botulinum Toxin Application for Treatment of Graft Vasospasm: A Reverse Translational Study

Area of Science:

• Vascular Surgery
• Neurosurgery
• Pharmacology

Background:

• Vascular graft vasospasm is a critical risk in revascularization and reconstructive surgery, potentially causing severe neurological issues.
• Cerebrovascular graft transplantation, used for conditions like Moyamoya disease, has a 5-10% risk of vasospasm.

Purpose of the Study:

• To evaluate the clinical outcomes of ex vivo botulinum toxin A (BoNT/A) treatment on arterial grafts.
• To investigate the underlying mechanisms by which BoNT/A reduces vasospasm.

Main Methods:

• Retrospective review of 63 patients undergoing surgery.
• Ex vivo studies on human vascular graft tissue treated with low-dose BoNT/A.
• Analysis of spasmolytic effectors: cleaved SNAP25, pMLC, pMYPT, ROCK1/2, and catecholamines.

Main Results:

• Low-dose BoNT/A treatment was associated with a significant reduction in clinical vasospasm (13.3%, p<0.05).
• No safety concerns were identified in patients receiving BoNT/A treated grafts.
• BoNT/A treatment increased cleaved SNAP25 and reduced pMLC, pMYPT, and catecholamine levels in grafts.

Conclusions:

• Ex vivo BoNT/A treatment of arterial grafts shows promise in reducing vasospasm during revascularization surgery.
• The mechanism involves pleiotropic vasodilatory pathways, including modulation of SNAP25 and catecholamine signaling.
• BoNT/A may have broad, safe applications as a spasmolytic agent across surgical specialties.