Effects of a novel, 3D printed bilateral arytenoid abductor on canine laryngeal airway resistance ex vivo.

BACKGROUND: Laryngeal paralysis is a disease process most commonly seen in older, large breed dogs. When both arytenoid cartilages are affected dogs can develop life-threatening respiratory compromise, therefore surgical intervention is recommended. While there are multiple surgical procedures that have been described to treat laryngeal paralysis, there remains a considerable risk for postoperative complications, most commonly aspiration pneumonia. The objective of this ex vivo experimental study was to evaluate the effects of a novel, 3D printed bilateral arytenoid abductor on laryngeal airway resistance in canine cadaver larynges. Laryngeal airway resistance was calculated for each specimen before (control) and after placement of a 3D printed, bilateral arytenoid abductor. The airway resistance was measured at an airflow of 10 L/min with the epiglottis closed and at airflows ranging from 15 L/min to 60 L/min with the epiglottis open. The effects of the bilateral arytenoid abductor on laryngeal airway resistance were evaluated statistically. RESULTS: With the epiglottis open, median laryngeal airway resistance in all larynges with a bilateral arytenoid abductor were significantly decreased at airflows of 15 L/min (0.0cmH2O/L/sec), 30 L/min (0.2cmH2O/L/sec), and 45 L/min (0.2cmH2O/L/sec) compared to the controls 15 L/min (0.4cmH2O/L/sec; P = 0.04), 30 L/min (0.9cmH2O/L/sec; P = 0.04), and 45 L/min (1.2cmH2O/L/sec; P = 0.04). When the epiglottis was closed, there was no significant difference in laryngeal resistance between the control (18.8cmH2O/L/sec) and the abducted larynges (18.1cmH2O/L/sec; P = 0.83). CONCLUSIONS: Placement of a bilateral arytenoid abductor reduced laryngeal resistance in canine cadaver larynges compared to the controls when the epiglottis was open. With the epiglottis closed, there was no loss of laryngeal resistance while the device abducted the arytenoid cartilages. The results of this ex vivo study is encouraging for consideration of further evaluation of the bilateral arytenoid abductor to determine an appropriate material and tolerance of this device in vivo.

T Cell Receptor-induced Nuclear Factor κB (NF-κB) Signaling and Transcriptional Activation Are Regulated by STIM1- and Orai1-mediated Calcium Entry.

T cell activation following antigen binding to the T cell receptor (TCR) involves the mobilization of intracellular Ca(2+) to activate the key transcription factors nuclear factor of activated T lymphocytes (NFAT) and NF-κB. The mechanism of NFAT activation by Ca(2+) has been determined. However, the role of Ca(2+) in controlling NF-κB signaling is poorly understood, and the source of Ca(2+) required for NF-κB activation is unknown. We demonstrate that TCR- but not TNF-induced NF-κB signaling upstream of IκB kinase activation absolutely requires the influx of extracellular Ca(2+) via STIM1-dependent Ca(2+) release-activated Ca(2+)/Orai channels. We further show that Ca(2+) influx controls phosphorylation of the NF-κB protein p65 on Ser-536 and that this posttranslational modification controls its nuclear localization and transcriptional activation. Notably, our data reveal that this role for Ca(2+) is entirely separate from its upstream control of IκBα degradation, thereby identifying a novel Ca(2+)-dependent distal step in TCR-induced NF-κB activation. Finally, we demonstrate that this control of distal signaling occurs via Ca(2+)-dependent PKCα-mediated phosphorylation of p65. Thus, we establish the source of Ca(2+) required for TCR-induced NF-κB activation and define a new distal Ca(2+)-dependent checkpoint in TCR-induced NF-κB signaling that has broad implications for the control of immune cell development and T cell functional specificity.