The contribution of the sympathetic nervous system (SNS) versus the parasympathetic nervous system (PSNS) in mediating fatal cardiac arrhythmias during insulin-induced severe hypoglycemia is not well understood. Therefore, experimental protocols were performed in nondiabetic Sprague-Dawley rats to test the SNS with 1) adrenal demedullation and 2) chemical sympathectomy, and to test the PSNS with 3) surgical vagotomy, 4) nicotinic receptor (mecamylamine) and muscarinic receptor (AQ-RA 741) blockade, and 5) ex vivo heart perfusions with normal or low glucose, acetylcholine (ACh), and/or mecamylamine. In protocols 1–4, 3-h hyperinsulinemic (0.2 units/kg/min) and hypoglycemic (10–15 mg/dL) clamps were performed. Adrenal demedullation and chemical sympathectomy had no effect on mortality or arrhythmias during severe hypoglycemia compared with controls. Vagotomy led to a 6.9-fold decrease in mortality; reduced first- and second-degree heart block 4.6- and 4-fold, respectively; and prevented third-degree heart block compared with controls. Pharmacological blockade of nicotinic receptors, but not muscarinic receptors, prevented heart block and mortality versus controls. Ex vivo heart perfusions demonstrated that neither low glucose nor ACh alone caused arrhythmias, but their combination induced heart block that could be abrogated by nicotinic receptor blockade. Taken together, ACh activation of nicotinic receptors via the vagus nerve is the primary mediator of severe hypoglycemia–induced fatal cardiac arrhythmias.

Central compartment atopic disease (CCAD) is a distinct phenotype within chronic rhinosinusitis with nasal polyps (CRSwNP) with a pathophysiology that bridges the gap between allergy and CRSwNP, an association that was previously ambiguous. Understanding this endotype and its link to allergic disease is crucial for improved CCAD management. Using a systematic search and an independent dual-reviewer evaluation and data extraction process, this scoping review examines the clinical features, management options, and treatment outcomes of CCAD. Central compartment (CC) polypoid changes of the MT predominantly correlate with allergic rhinitis, increased septal inflammation, oblique MT orientation, and decreased nasal cavity opacification and Lund–Mackay scores compared to other CRSwNP subtypes. CCAD patients also exhibit higher rates of asthma, allergen sensitization, and hyposmia or anosmia. Surgical outcomes, including revision rate and SNOT-22 improvement, are favorable in CCAD as well. In conclusion, CCAD primarily affects atopic individuals and is managed using endoscopic sinus surgery combined with treating the underlying allergy. Continued research is needed to further refine understanding and develop optimal treatment strategies of this emerging CRS subtype.

For people with type 1 diabetes, severe hypoglycemia can be fatal. We show in our animal model that insulin-deficient diabetic rats have fatal cardiac arrhythmias during severe hypoglycemia that are associated with increased cardiac oxidative stress. Importantly, treatment with vitamin E, to reduce oxidative stress, decreased fatal cardiac arrhythmias during severe hypoglycemia.