Faculty Bibliography

BACKGROUND:The etiologies of intraoperative cardiac arrest within otolaryngology are not well understood as they are rare events. METHODS:A comprehensive review of the etiologies and corresponding pathophysiologic neural mechanisms of intraoperative cardiac arrest in otolaryngologic surgery are examined. RESULTS:The occurrence of this rare complication has been described in a range of head and neck procedures, including but not limited to suspension laryngoscopy and oncologic resections in the neck, maxilla and thyroid. Three anatomically distinct pathways leading to intraoperative cardiac arrest are described: direct vagal stimulation, the trigeminocardiac reflex and the baroreceptor reflex. All three share the final common pathway of parasympathetic signaling to the sinoatrial node via the cardiac fibers of the vagus nerve. CONCLUSION:With a firm understanding of the mechanistic underpinning of this rare phenomenon, otolaryngologic surgeons can be better prepared for its occurrence.

An intact kidney filter is vital to retention of essential proteins in the blood and removal of waste from the body. Damage to the filtration barrier results in albumin loss in the urine, a hallmark of cardiovascular disease and kidney failure. Here we found that the ion channel TRPC5 mediates filtration barrier injury. Using Trpc5-KO mice, a small-molecule inhibitor of TRPC5, Ca2+ imaging in isolated kidney glomeruli, and live imagining of podocyte actin dynamics, we determined that loss of TRPC5 or its inhibition abrogates podocyte cytoskeletal remodeling. Inhibition or loss of TRPC5 prevented activation of the small GTP-binding protein Rac1 and stabilized synaptopodin. Importantly, genetic deletion or pharmacologic inhibition of TRPC5 protected mice from albuminuria. These data reveal that the Ca2+-permeable channel TRPC5 is an important determinant of albuminuria and identify TRPC5 inhibition as a therapeutic strategy for the prevention or treatment of proteinuric kidney disease.