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Several human studies have associated nitric oxide administration via the cardiopulmonary bypass circuit with decreased incidence of cardiopulmonary bypass–associated acute kidney injury, but histopathologic and serologic evidence of nitric oxide efficacy for acute kidney injury attenuation are lacking. By using a survival ovine model (72 hours), acute kidney injury was induced by implementing low-flow cardiopulmonary bypass for 2 hours, followed by full-flow cardiopulmonary bypass for 2 hours. The nitric oxide cohort (n = 6) received exogenous nitric oxide through the cardiopulmonary bypass circuit via the oxygenator, and the control group (n = 5) received no nitric oxide. Serial serologic biomarkers and renal histopathology were obtained. Baseline characteristics (age, weight) and intraoperative parameters (cardiopulmonary bypass time, urine output, heart rate, arterial pH, and lactate) were equivalent (P >.10) between groups. Postoperatively, urine output, heart rate, respiratory rate, and peripheral arterial saturation were equivalent (P >.10) between groups. Post–cardiopulmonary bypass creatinine elevations from baseline were significantly greater in the control group versus the nitric oxide group at 16, 24, and 48 hours (all P <.05). Histopathologic evidence of moderate/severe acute kidney injury (epithelial necrosis, tubular slough, cast formation, glomerular edema) occurred in 60% (3/5) of the control group versus 0% (0/6) of the nitric oxide group. Cortical tubular epithelial cilia lengthening (a sensitive sign of cellular injury) was significantly greater in the control group than in the nitric oxide group (P =.012). In a survival ovine cardiopulmonary bypass model, nitric oxide administered with cardiopulmonary bypass demonstrated serologic and histologic evidence of renal protection from acute kidney injury. These results provide insight into 1 potential mechanism for cardiopulmonary bypass–associated acute kidney injury and supports continued study of nitric oxide via cardiopulmonary bypass circuit for prevention of acute kidney injury. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To develop a reproducible and consistent chronic subglottic stenosis (SGS) in an endoscopic animal model. Study Design: Prospective study. Methods: We conducted a prospective study using New Zealand white rabbits. Chronic SGS was induced endoscopically by Bugbee electrocautery to 50% to 75% of the subglottic area's circumference, followed by 4‐hour endotracheal intubation. The rabbit airways were endoscopically assessed and sized with uncuffed endotracheal tubes (ETTs) before the injury, during follow‐up, and at the endpoints. There were four endpoints: 2, 4, 6, and 8 weeks post SGS induction. Animals were humanely euthanized for histopathological examination of the subglottic injury site and microscopic measurement of the cricoid lumen. Results: Twenty‐two rabbits reached the endpoints, and 18 rabbits developed chronic SGS. ETT size significantly decreased by 0.5 from preinjury to the endpoint in all groups, P <.001. Control median cricoid lumen measurements were 20.48 mm2, the median cricoid lumen measurement for the 2 weeks endpoint was 14.3 mm2, 4 weeks 11.69 mm2, 6 weeks 16.03 mm2, and 8 weeks endpoint median was 16.33 mm2. Histopathological examination showed chronic scar tissue and new cartilage formation at the cricoid level, mainly at the posterior subglottic injury site starting from 4 weeks postinjury. Collagen staining revealed substantial amounts of organized collagen and different collagen orientation starting 4 weeks postinjury lasting until 8 weeks postinjury. Conclusion: We developed an animal model to study chronic SGS. This model will be utilized to compare different endoscopic treatment interventions in acute SGS versus chronic SGS and further define the molecular basis of SGS. Level of Evidence: NA Laryngoscope, 132:1909–1915, 2022 [ABSTRACT FROM AUTHOR]

Abstract: Human arginase deficiency is characterized by hyperargininemia and infrequent episodes of hyperammonemia, which lead to neurological impairment with spasticity, loss of ambulation, seizures, and severe mental and growth retardation; uncommonly, patients suffer early death from this disorder. In a murine targeted knockout model, onset of the phenotypic abnormality is heralded by weight loss at around day 15, and death occurs typically by postnatal day 17 with hyperargininemia and markedly elevated ammonia. This discrepancy between the more attenuated juvenile-onset human disease and the lethal neonatal murine model has remained suboptimal for studying and developing therapy for the more common presentation of arginase deficiency. These investigations aimed to address this issue by creating an adult conditional knockout mouse to determine whether later onset of arginase deficiency also resulted in lethality. Animal survival and ammonia levels, body weight, circulating amino acids, and tissue arginase levels were examined as outcome parameters after widespread Cre-recombinase activation in a conditional knockout model of arginase 1 deficiency. One hundred percent of adult female and 70% of adult male mice died an average of 21.0 and 21.6days, respectively, after the initiation of tamoxifen administration. Animals demonstrated elevated circulating ammonia and arginine at the onset of phenotypic abnormalities. In addition, brain and liver amino acids demonstrated abnormalities. These studies demonstrate that (a) the absence of arginase in adult animals results in a disease profile (leading to death) similar to that of the targeted knockout and (b) the phenotypic abnormalities seen in the juvenile-onset model are not exclusive to the age of the animal but instead to the biochemistry of the disorder. This adult model will be useful for developing gene- and cell-based therapies for this disorder that will not be limited by the small animal size of neonatal therapy and for developing a better understanding of the characteristics of hyperargininemia. [Copyright &y& Elsevier]