Quantification of rat supraglottic laryngeal sensation threshold.

OBJECTIVE: Laryngeal adductor response (LAR) to air puff is used as a reliable method in evaluating sensation thresholds (ST) in human laryngeal sensory disorders. This method has been difficult to perform in small subjects such as rodents. The aims of this study were to 1) evaluate ST to air puff under binocular microlaryngoscopy in rats to evaluate laryngeal sensory disorders, 2) determine sensory thresholds at varying target locations, and 3) determine the ideal depth of anesthesia. STUDY DESIGN: Animal study. METHODS: Rats were induced with ketamine/xylazine. The level of anesthesia was monitored by spontaneous glottic closure and corneal reflex testing. Air puffs were delivered to the epiglottis, arytenoid, and piriform sinus at varied pressures with pulse time kept constant. Sensation thresholds were determined by direct visualization of the larynx using a binocular microscope. Topical lidocaine was then applied to the larynx and ST was determined. Trials were repeated in a small subset of animals. RESULTS: Twenty-six trials were performed in 14 rats. Mean STs were 39 ± 9.7 mm Hg at the epiglottis, 48.8 ± 10.5 at the arytenoid, and not detectable at the pyriform sinus. Repeated trials demonstrated consistent results. Lidocaine effectively ablated the LAR in each trial. The LAR was difficult to induce while corneal reflex was absent and was difficult to distinguish from spontaneous glottic closures while under lighter sedation. CONCLUSION: Air pulse stimulation in rats is a simple, reliable, and effective way to determine laryngopharyngeal STs in rats and can be used as an efficient and affordable method for experimentation involving laryngeal sensory disorders. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E265-E269, 2017.

Compound motor action potential duration and latency are markers of recurrent laryngeal nerve injury.

OBJECTIVE: Compound motor action potential (CMAP) can quantitatively evaluate innervation following injury to the recurrent laryngeal nerve (RLN) in canines. CMAP duration (the total time of CMAP) and latency (the time between the nerve impulse and the onset of action potentials) have not been assessed following RLN injury. STUDY DESIGN: Animal study. METHODS: Twelve canine hemilaryngeal preparations were investigated. Baseline CMAP duration and latency were derived. Group A (n = 5) underwent RLN stretch injury, and group B (n = 7) underwent RLN transection/repair. The change in CMAP duration and latency was assessed between the baseline and 6-month measurements using receiver operator characteristic (ROC) curves for each group individually and combined. RESULTS: Six months following injury, transection/repair injuries had the most significant increase in CMAP duration (2.8 ± 0.6 ms vs. 4.2 ± 0.8 ms, difference 1.4 ms 95% confidence interval [CI]: 0.43 to 2.40) and latency (2.6 ± 0.5 ms vs. 5.6 ± 1.5 ms, difference 3.0 ms 95% CI: 1.65 to 4.38). Stretch injuries also caused an increase in CMAP duration (2.3 ± 0.8 ms vs. 3.0 ± 0.6 ms, difference 0.7 ms 95% CI: -0.49 to 1.77) and latency (2.5 ± 0.8 ms vs. 4.7 ± 1.5 ms, difference 2.3 95% CI: 0.76 to 3.80). Using ROC curves, CMAP duration and latency differentiated between the baseline control and RLN injury at 6 months (area under the curve = 0.78 and 0.98, respectively). CONCLUSION: CMAP duration and latency are both quantitative measures that may have clinical utility as markers of RLN injury. CMAP latency had superior discrimination between injured and uninjured RLNs. Increased CMAP duration and latency may be explained by incomplete myelination and focal conduction block. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:1855-1860, 2017.

Potassium titanyl phosphate laser welding following complete nerve transection.

OBJECTIVES/HYPOTHESIS: Cranial nerve transection during head and neck surgery is conventionally repaired by microsuture reanastomosis. Laser nerve welding (LNW), using CO2 laser to spot-weld the epineurium of transected nerve endings, has been shown in animal models to be a novel alternative to microsuture repair. This method avoids needle/suture material and minimizes instrumentation of the nerve. We hypothesized that potassium titanyl phosphate (KTP) laser would be superior to CO2 laser in repairing transected nerves. Using a rat posterior tibial nerve injury model, we compared CO2 laser, KTP laser, and microsuture reanastomosis. STUDY DESIGN: Animal study. METHODS: Animals underwent unilateral posterior tibial nerve transection. The injury was repaired by microsuture repair (n = 15), CO2 laser repair (n = 15), or KTP laser repair (n = 15). Weekly walking tracks were performed to measure functional recovery. Nerve segments were harvested for axon counting. RESULTS: At 6 weeks, the KTP LNW had the best functional recovery (92.4 ± 8.6%) compared to microsuture repair (84.5 ± 10.2%, difference 7.9%, 95% confidence interval [CI]: 0.84%-14.96%). CO2 laser repair had a functional recovery of 86.8 ± 11.2%. KTP LNW had better axon recovery compared to transection/repair (difference 530.7 axons, 95% CI: 329.9-731.5). Operative time for the microsuture repair was 18.2 ± 6.8 minutes, compared to 5.8 ± 3.7 minutes for the LNW groups (difference 12.4 minutes, 95% CI: 8.6-16.2 minutes). CONCLUSIONS: KTP, CO2 , and microsuture repair all showed good functional recovery following complete transection of the posterior tibial nerve. Following complete nerve transection during head and neck surgery, KTP LNW may be a novel alternative to microsuture repair. LEVEL OF EVIDENCE: NA Laryngoscope, 127:1525-1530, 2017.

Surgical Treatment of Vestibular Schwannoma: Does Age Matter?

OBJECTIVE: For older patients (>65 years) who undergo surgical treatment of vestibular schwannoma (VS), the reported rates of facial nerve preservation, hearing preservation, and complications are inconsistent. Many surgeons believe that older patients have worse outcomes than their younger counterparts and advise against surgical treatment. We analyzed a consecutive series of patients with VS treated with surgery to determine whether age was a factor in outcome. METHODS: We retrospectively reviewed all patients treated for VS at our institution from January 1, 2000, to July 1, 2012. We examined how sex, age (≥65 years and <65 years), race, tumor size, tumor laterality, body mass index, Charlson Comorbidity Index, smoking status, surgical approach, and preoperative hearing and symptoms were associated with outcomes. RESULTS: Two-hundred forty-three patients underwent resection of VS, including 23 patients ≥65 years (mean 68 ± 4 years) and 220 patients <65 years (mean 47 ± 11 years). The average tumor size was 16.5 mm. Older patients had a significantly lower body mass index of 26.6 vs. 29.8 (P = 0.03) and were more likely to have a CCI ≥2 (52.2% vs. 18.2%, P ≤ 0.00, preoperative facial numbness (34.8% vs. 10.1%, P = 0.03), and dizziness (78.3% vs. 49.3%, P = 0.03). There were no significant differences after surgery in facial nerve outcome, hearing preservation outcome, or general surgical complications between the 2 cohorts. CONCLUSIONS: With no difference in surgical complications, facial nerve outcome, or hearing preservation rates between older and younger patients in our series, age alone may not be an absolute contraindication to surgical management of VS.

Assessment of otolaryngic knowledge in primary care residents.

OBJECTIVES: (1) Determine the amount of exposure to otolaryngology in medical training of non-otolaryngology residents. (2) Evaluate the general otolaryngic knowledge in these residents. STUDY DESIGN: Cross-sectional survey. SETTING: Academic medical center. SUBJECTS AND METHODS: A 10-question multiple-choice quiz was given to residents in family practice, pediatrics, emergency medicine, and internal medicine during scheduled educational conferences. Residents were also asked if they ever participated in an otolaryngology rotation during medical school or residency. Medical students and otolaryngology residents completed the quiz to act as controls. RESULTS: A total of 98 examinations were analyzed (49 non-otolaryngology residents, 10 otolaryngology residents, and 39 second-year medical students). Only 24% of the non- otolaryngology residents had an otolaryngology rotation during medical school. The same amount (24%) had a rotation during residency. The average percentage correct on the quiz was 48%, 56%, and 92% for medical students, non-otolaryngology, and otolaryngology residents, respectively (P < 0.05). Questions with surprising results included one with an endoscopic image of the middle turbinate and examinees asked to identify the structure (non-otolaryngology residents = 18% correct). A laryngectomy stoma was shown and participants asked what would happen if the stoma was occluded for 10 minutes (non-otolaryngology residents = 20% correct). CONCLUSION: In this sample of non-otolaryngology residents, a minority experienced a clinical rotation in otolaryngology during medical school or residency. This nonvalidated questionnaire also suggested significant deficiencies in basic otolaryngic knowledge in these residents. Identifying mechanisms to improve exposure to otolaryngology in the medical training curriculum is needed.

Ceramide mediates vascular dysfunction in diet-induced obesity by PP2A-mediated dephosphorylation of the eNOS-Akt complex.

Vascular dysfunction that accompanies obesity and insulin resistance may be mediated by lipid metabolites. We sought to determine if vascular ceramide leads to arterial dysfunction and to elucidate the underlying mechanisms. Pharmacological inhibition of de novo ceramide synthesis, using the Ser palmitoyl transferase inhibitor myriocin, and heterozygous deletion of dihydroceramide desaturase prevented vascular dysfunction and hypertension in mice after high-fat feeding. These findings were recapitulated in isolated arteries in vitro, confirming that ceramide impairs endothelium-dependent vasorelaxation in a tissue-autonomous manner. Studies in endothelial cells reveal that de novo ceramide biosynthesis induced protein phosphatase 2A (PP2A) association directly with the endothelial nitric oxide synthase (eNOS)/Akt/Hsp90 complex that was concurrent with decreased basal and agonist-stimulated eNOS phosphorylation. PP2A attenuates eNOS phosphorylation by preventing phosphorylation of the pool of Akt that colocalizes with eNOS and by dephosphorylating eNOS. Ceramide decreased the association between PP2A and the predominantly cytosolic inhibitor 2 of PP2A. We conclude that ceramide mediates obesity-related vascular dysfunction by a mechanism that involves PP2A-mediated disruption of the eNOS/Akt/Hsp90 signaling complex. These results provide important insight into a pathway that represents a novel target for reversing obesity-related vascular dysfunction.

Contribution of insulin and Akt1 signaling to endothelial nitric oxide synthase in the regulation of endothelial function and blood pressure.

Impaired insulin signaling via phosphatidylinositol 3-kinase/Akt to endothelial nitric oxide synthase (eNOS) in the vasculature has been postulated to lead to arterial dysfunction and hypertension in obesity and other insulin resistant states. To investigate this, we compared insulin signaling in the vasculature, endothelial function, and systemic blood pressure in mice fed a high-fat (HF) diet to mice with genetic ablation of insulin receptors in all vascular tissues (TTr-IR(-/-)) or mice with genetic ablation of Akt1 (Akt1-/-). HF mice developed obesity, impaired glucose tolerance, and elevated free fatty acids that was associated with endothelial dysfunction and hypertension. Basal and insulin-mediated phosphorylation of extracellular signal-regulated kinase 1/2 and Akt in the vasculature was preserved, but basal and insulin-stimulated eNOS phosphorylation was abolished in vessels from HF versus lean mice. In contrast, basal vascular eNOS phosphorylation, endothelial function, and blood pressure were normal despite absent insulin-mediated eNOS phosphorylation in TTr-IR(-/-) mice and absent insulin-mediated eNOS phosphorylation via Akt1 in Akt1-/- mice. In cultured endothelial cells, 6 hours of incubation with palmitate attenuated basal and insulin-stimulated eNOS phosphorylation and NO production despite normal activation of extracellular signal-regulated kinase 1/2 and Akt. Moreover, incubation of isolated arteries with palmitate impaired endothelium-dependent but not vascular smooth muscle function. Collectively, these results indicate that lower arterial eNOS phosphorylation, hypertension, and vascular dysfunction following HF feeding do not result from defective upstream signaling via Akt, but from free fatty acid-mediated impairment of eNOS phosphorylation.