Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral and anal sphincter function. Part 4: Effectiveness of the motor reinnervation.

In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. Twelve months postdecentralization, eight underwent transfer of obturator nerve branches to pelvic nerve vesical branches, and sciatic nerve branches to pudendal nerves, followed by 10 mo recovery (ObNT-ScNT Reinn). The remaining four were euthanized 18 mo postdecentralization (Decentralized). Results were compared with 18 Controls. Squat-and-void postures were tracked during awake cystometry. None showed squat-and-void postures during the decentralization phase. Seven of eight ObNT-ScNT Reinn began showing such postures by 6 mo postreinnervation; one showed a return of defecation postures. Retrograde dyes were injected into the bladder and urethra 3 wk before euthanasia, at which point, roots and transferred nerves were electrically stimulated to evaluate motor function. Upon L2-L6 root stimulation, five of eight ObNT-ScNT Reinn showed elevated detrusor pressure and four showed elevated urethral pressure, compared with L7-S3 root stimulation. After stimulation of sciatic-to-pudendal transferred nerves, three of eight ObNT-ScNT Reinn showed elevated urethral pressure; all showed elevated anal sphincter pressure. Retrogradely labeled neurons were observed in L2-L6 ventral horns (in laminae VI, VIII, and IX) of ObNT-ScNT Reinn versus Controls in which labeled neurons were observed in L7-S3 ventral horns (in lamina VII). This data supports the use of nerve transfer techniques for the restoration of bladder function.NEW & NOTEWORTHY This data supports the use of nerve transfer techniques for the restoration of bladder function.

Anatomical Location of the Vesical Branches of the Inferior Hypogastric Plexus in Human Cadavers.

We have demonstrated in canines that somatic nerve transfer to vesical branches of the inferior hypogastric plexus (IHP) can be used for bladder reinnervation after spinal root injury. Yet, the complex anatomy of the IHP hinders the clinical application of this repair strategy. Here, using human cadavers, we clarify the spatial relationships of the vesical branches of the IHP and nearby pelvic ganglia, with the ureteral orifice of the bladder. Forty-four pelvic regions were examined in 30 human cadavers. Gross post-mortem and intra-operative approaches (open anterior abdominal, manual laparoscopic, and robot-assisted) were used. Nerve branch distances and diameters were measured after thorough visual inspection and gentle dissection, so as to not distort tissue. The IHP had between 1 to 4 vesical branches (2.33 ± 0.72, mean ± SD) with average diameters of 0.51 ± 0.06 mm. Vesical branches from the IHP arose from a grossly visible pelvic ganglion in 93% of cases (confirmed histologically). The pelvic ganglion was typically located 7.11 ± 6.11 mm posterolateral to the ureteral orifice in 69% of specimens. With this in-depth characterization, vesical branches from the IHP can be safely located both posterolateral to the ureteral orifice and emanating from a more proximal ganglionic enlargement during surgical procedures.

Characterization of pain-related behaviors in a rat model of acute-to-chronic low back pain: single vs. multi-level disc injury.

Introduction: Low back pain is the most common type of chronic pain. We examined pain-related behaviors across 18 weeks in rats that received injury to one or two lumbar intervertebral discs (IVD) to determine if multi-level disc injuries enhance/prolong pain. Methods: Twenty-three Sprague-Dawley adult female rats were used: 8 received disc puncture (DP) of one lumbar IVD (L5/6, DP-1); 8 received DP of two lumbar IVDs (L4/5 & L5/6, DP-2); 8 underwent sham surgery. Results: DP-2 rats showed local (low back) sensitivity to pressure at 6- and 12-weeks post-injury, and remote sensitivity to pressure (upper thighs) at 12- and 18-weeks and touch (hind paws) at 6, 12 and 18-weeks. DP-1 rats showed local and remote pressure sensitivity at 12-weeks only (and no tactile sensitivity), relative to Sham DP rats. Both DP groups showed reduced distance traveled during gait testing over multiple weeks, compared to pre-injury; only DP-2 rats showed reduced distance relative to Sham DP rats at 12-weeks. DP-2 rats displayed reduced positive interactions with a novel adult female rat at 3-weeks and hesitation and freezing during gait assays from 6-weeks onwards. At study end (18-weeks), radiological and histological analyses revealed reduced disc height and degeneration of punctured IVDs. Serum BDNF and TNFα levels were higher at 18-weeks in DP-2 rats, relative to Sham DP rats, and levels correlated positively with remote sensitivity in hind paws (tactile) and thighs (pressure). Discussion: Thus, multi-level disc injuries resulted in earlier, prolonged and greater discomfort locally and remotely, than single-level disc injury. BDNF and TNFα may have contributing roles.

A new model of arteriovenous fistula to study hemodialysis access complications.

PURPOSE: This report presents a new animal model of arteriovenous fistula (AVF) with attention given to surgical techniques as well as hemodynamic and pathologic measurements. Of note, this model was created with a tunneled central catheter with the purpose of studying therapeutic interventions, including hemodialysis. METHODS: Side-common carotid artery to end-external jugular vein AVFs were created in eight minipigs. A tunneled central catheter was also placed in the internal jugular vein. After 28 days, hemodynamic measurements of AVF flow and stenosis were performed. The minipigs were then euthanized and the AVFs were harvested for pathologic measurements of neointimal hyperplasia and thrombus volumes. In order to account for variable size of the AVFs, percentage luminal stenosis and degree of intima-media thickening were calculated. RESULTS: After 28 days, all eight AVFs remained patent. On average, 19% of arterial blood flow that approached the AVF traveled through the anastomosis. The average luminal stenosis by angiogram was 61.1%. The average neointimal hyperplasia and thrombus volumes were 1.4×10(8) and 3.8×10(8) µm3, respectively. The average luminal stenosis and intima-media thickening were 65.2% and 430.4 µm, respectively. CONCLUSIONS: This AVF model is ideal because of the relative ease of surgery and husbandry, lack of complications, as well as consistent and rapid development of the neointimal lesion which underlies AVF failure.

Examining prehospital intubation for penetrating trauma in a swine hemorrhagic shock model.

BACKGROUND: Prehospital intubation does not result in a survival advantage in patients experiencing penetrating trauma, yet resistance to immediate transportation to facilitate access to definitive care remains. An animal model was developed to determine whether intubation provides a survival advantage during severe hemorrhagic shock. We hypothesized that intubation would not provide a survival advantage in potentially lethal hemorrhage. METHODS: After starting a propofol drip, Yorkshire pigs were intubated (n = 6) or given bag-valve mask ventilation (n = 7) using 100% oxygen. The carotid artery was cannulated with a 14-gauge catheter, and a Swan-Ganz catheter was placed under fluoroscopy using a central venous introducer. After obtaining baseline hemodynamic and laboratory data, the animals were exsanguinated through the carotid line until death. The primary end point was time until death, while secondary end points included volume of blood shed, temperature, cardiac index, mean arterial pressure, lactic acid, base excess, and creatinine levels measured in 10-minute intervals. RESULTS: There was no difference in time until death between the two groups (51.1 [2.5] minutes vs. 48.5 [2.4] minutes, p = 0.52). Intubated animals had greater volume of blood shed at 30 minutes (33.6 [4.4] mL/kg vs. 28.5 [4.3] mL/kg, p = 0.03), 40 minutes (41.7 [4.7] mL/kg vs. 34.9 [3.8] mL/kg, p = 0.04), and 50 minutes (49.2 [8.6] mL/kg vs. 40.2 [1.0] mL/kg, p = 0.001). In addition, the intubated animals were more hypothermic at 40 minutes (35.5°C [0.4°C] vs. 36.7°C [0.2°C], p = 0.01) and had higher lactate levels (2.4 [0.1] mmol/L vs. 1.8 [0.4] mmol/L, p = 0.04) at 10 minutes. Cardiac index (p = 0.66), mean arterial pressure (p = 0.69), base excess (p = 0.14), and creatinine levels (p = 0.37) were not different throughout the shock phase. CONCLUSION: Intubation does not convey a survival advantage in this model of severe hemorrhagic shock. Furthermore, intubation in the setting of severe hemorrhagic shock may result in a more profuse hemorrhage, worse hypothermia, and higher lactate when compared with bag-valve mask ventilation.