SmartPill™ Administration to Assess Gastrointestinal Function after Spinal Cord Injury in a Porcine Model-A Preliminary Study.

Gastrointestinal (GI) complications, including motility disorders, metabolic deficiencies, and changes in gut microbiota following spinal cord injury (SCI), are associated with poor outcomes. After SCI, the autonomic nervous system becomes unbalanced below the level of injury and can lead to severe GI dysfunction. The SmartPill™ is a non-invasive capsule that, when ingested, transmits pH, temperature, and pressure readings that can be used to assess effects in GI function post-injury. Our minipig model allows us to assess these post-injury changes to optimize interventions and ultimately improve GI function. The aim of this study was to compare pre-injury to post-injury transit times, pH, and pressures in sections of GI tract by utilizing the SmartPill™ in three pigs after SCI at 2 and 6 weeks. Tributyrin was administered to two pigs to assess the influences on their gut microenvironment. We observed prolonged GET (Gastric Emptying Time) and CTT (Colon Transit Time), decreases in contraction frequencies (Con freq) in the antrum of the stomach, colon, and decreases in duodenal pressures post-injury. We noted increases in Sum amp generated at 2 weeks post-injury in the colon, with corresponding decreases in Con freq. We found transient changes in pH in the colon and small intestine at 2 weeks post-injury, with minimal effect on stomach pH post-injury. Prolonged GETs and CTTs can influence the absorptive profile in the gut and contribute to pathology development. This is the first pilot study to administer the SmartPill™ in minipigs in the context of SCI. Further investigations will elucidate these trends and characterize post-SCI GI function.

Characterization of Lower Urinary Tract Dysfunction after Thoracic Spinal Cord Injury in Yucatan Minipigs.

There is an increasing need to develop approaches that will not only improve the clinical management of neurogenic lower urinary tract dysfunction (NLUTD) after spinal cord injury (SCI), but also advance therapeutic interventions aimed at recovering bladder function. Although pre-clinical research frequently employs rodent SCI models, large animals such as the pig may play an important translational role in facilitating the development of devices or treatments. Therefore, the objective of this study was to develop a urodynamics protocol to characterize NLUTD in a porcine model of SCI. An iterative process to develop the protocol to perform urodynamics in female Yucatan minipigs began with a group of spinally intact, anesthetized pigs. Subsequently, urodynamic studies were performed in a group of awake, lightly restrained pigs, before and after a contusion-compression SCI at the T2 or T9-T11 spinal cord level. Bladder tissue was obtained for histological analysis at the end of the study. All anesthetized pigs had bladders that were acontractile, which resulted in overflow incontinence once capacity was reached. Uninjured, conscious pigs demonstrated appropriate relaxation and contraction of the external urethral sphincter during the voiding phase. SCI pigs demonstrated neurogenic detrusor overactivity and a significantly elevated post-void residual volume. Relative to the control, SCI bladders were heavier and thicker. The developed urodynamics protocol allows for repetitive evaluation of lower urinary tract function in pigs at different time points post-SCI. This technique manifests the potential for using the pig as an intermediary, large animal model for translational studies in NLUTD.

Treadmill-Based Gait Kinematics in the Yucatan Mini Pig.

Yucatan miniature pigs (YMPs) are similar to humans in spinal cord size as well as physiological and neuroanatomical features, making them a useful model for human spinal cord injury. However, little is known regarding pig gait kinematics, especially on a treadmill. In this study, 12 healthy YMPs were assessed during bipedal and/or quadrupedal stepping on a treadmill at six speeds (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 km/h). Kinematic parameters, including limb coordination and proximal and distal limb angles, were measured. Findings indicate that YMPs use a lateral sequence footfall pattern across all speeds. Stride and stance durations decreased with increasing speed whereas swing duration showed no significant change. Across all speeds assessed, no significant differences were noted between hindlimb stepping parameters for bipedal or quadrupedal gait with the exception of distal limb angular kinematics. Specifically, significant differences were observed between locomotor tasks during maximum flexion (quadrupedal > bipedal), total excursion (bipedal > quadrupedal), and the phase relationship between the timing of maximum extension between the right and left hindlimbs (bipedal > quadrupedal). Speed also impacted maximum flexion and right-left phase relationships given that significant differences were found between the fastest speed (3.5 km/h) relative to each of the other speeds. This study establishes a methodology for bipedal and quadrupedal treadmill-based kinematic testing in healthy YMPs. The treadmill approach used was effective in recruiting primarily the spinal circuitry responsible for the basic stepping patterns as has been shown in cats. We recommend 2.5 km/h (0.7 m/sec) as a target walking gait for pre-clinical studies using YMPs, which is similar to that used in cats.