No abstract

No abstract

Summary:Palatal fistula between the oral and nasal cavities occurs in about 20% of palatal repairs after oncologic resection. Although healing by secondary intention may be employed as an initial strategy, persistent nonhealing symptomatic fistula necessitates intervention. Folded free flap used for primary repair of palatectomy defects enables placement of epithelialized tissue on both the oral and nasal cavities. In case of acquired palatal fistula, a turnover flap can be easily created, based on the free margin of the folded forearm free flap to serve as a reconstructive lifeboat.

Afferent and efferent fibers in the vagus travel inside nerve fascicles and form branches to innervate organs and regulate organ functions. The organization of fibers and fascicles in the vagus trunk, with respect to the functions they mediate and the organs they innervate, remains largely unknown. Accordingly, it is unknown whether that anatomical organization can be leveraged by bioelectronic devices for function- and organ-specific neuromodulation. To characterize the microscopic functional anatomy of the vagus we developed a pipeline consisting of micro-computed tomography-based morphometry of fascicles and quantitative immunohistochemistry of single fibers. We found that, in the swine vagus, fascicles form clusters specific to afferent and efferent functions, increasingly separated in the rostral direction, and other clusters specific to the innervated organs, including larynx, lungs and heart, increasingly separated in the caudal direction. Large myelinated and small unmyelinated efferents have small counts, cover large area of the nerve, and are limited to specific fascicles; small unmyelinated afferents have large counts, cover small area, and are uniformly distributed across fascicles. To test whether fiber populations can be selectively modulated, we developed a multi-contact cuff electrode that observes the fascicular vagus anatomy. Targeting of different nerve sub-sections evokes compound action potentials from different fiber types and elicits differential organ responses, including laryngeal muscle contraction, cough reflex, and changes in breathing and heart rate. Our results indicate that vagus fibers are spatially clustered according to functions they mediate and organs they innervate and can be differentially modulated by spatially selective nerve stimulation.

Cervical vagus nerve stimulation (VNS) provides relatively minimally-invasive access to vagal fiber populations innervating most visceral organs, making it an attractive therapy candidate for various diseases. To maximize desired and minimize off-target effects, VNS should be delivered in a fiber-selective manner. We sought to select and optimize parameters that preferentially activate large, intermediate or small-size vagal fibers in 2 animal species, rats and mice. We manipulated stimulus waveform and frequency of short-duration (10-s) stimulus trains (SSTs) at different intensities and measured fiber-specific stimulus-elicited compound action potentials, corresponding cardiorespiratory vagally-mediated responses and neuronal expression of c-FOS in sensory and motor brainstem nuclei. We compiled selectivity indices from those measurements to determine optimal parameters for each fiber type. Large- and intermediate-size fibers are activated by SSTs of 30 Hz frequency, using short-square and long-square or quasi-trapezoidal pulses, respectively, at different optimal intensities for different animals. Small-size fibers are activated by SSTs of frequencies >8KH at high stimulus intensities; using a computational model of vagal fibers we find that sodium channels may underlie this effect. All findings were consistent between rats and mice. Our study provides a robust design and optimization framework for targeting vagal fiber populations for improved safety and efficacy of VNS therapies.