Prevention of anastomotic thrombosis by botulinum toxin B after acute injury in a rat model

Abstract

Purpose: Revascularized or replanted digits may fail because of vessel thrombosis. Off-label use of botulinum toxin type A injected subcutaneously has been used successfully in limited case series to treat vasospastic disorders. Botulinum toxin type B (BTX-B) is thought to have an earlier onset of action than type A in certain settings. We used a rat model to determine the ability of BTX-B to decrease vasospasm and prevent thrombosis after acute vessel division and anastomotic repair.

Methods: We transected and immediately repaired the bilateral femoral arteries and veins of 25 rats via microscopic technique. We measured each vessel's diameter before transection. Each rat had 1 leg randomly assigned to receive BTX-B; the contralateral side received normal saline. We separated the animals into 5 groups. Each group underwent vasospastic stress at a different time point (12, 24, 48, 72, and 120 h) after the anastomoses and treatment with BTX-B or saline. Vasospastic stress included a lower extremity cold temperature challenge and systemic treatment with phenylephrine. After vasospastic stress, we reopened the wounds and recorded vessel thrombosis and diameter.

Results: Vessel thrombosis rate was lower in the BTX-B-treated group of vessels compared with those receiving placebo. Thrombosis rate was 8% for BTX-B-treated arteries versus 68% for saline-treated arteries. Thrombosis rate was 20% for BTX-B-treated veins versus 76% for saline-treated veins. Overall vessel thrombosis rate was significantly lower for BTX-B at all time points except at 120 hours when no thrombotic events occurred for either group. Average increase in diameter for BTX-B-treated vessels was significantly greater than that for the controls regardless of patency.

Conclusions: BTX-B prevented or reduced the incidence of thrombosis after acute vessel anastomosis in this rat model at all time points less than 120 hours compared with placebo. The average final vessel diameter throughout the series of BTX-B-treated vessels was significantly larger than in the control group.

Clinical relevance: The use of BTX-B may improve the success rate of microvascular anastomoses by being protective against vasospastic stress and subsequent thrombosis.