Transcriptomic-Metabolomic Profiling in Mouse Lung Tissues Reveals Sex- and Strain-Based Differences.

Omics analyses are commonly used for identifying pathways and genes responsible for physiologic and pathologic processes. Though sex is considered a biological variable in rigorous assessments of pulmonary responses to oxidant exposures, the contribution of the murine strain is largely ignored. This study utilized an unbiased integrated assessment of high-resolution metabolomic profiling and RNA-sequencing to explore sex- and strain-dependent pathways in adult mouse lungs. The results indicated that strain exhibited a greater influence than sex on pathways associated with inflammatory and oxidant/antioxidant responses and that interaction metabolites more closely resembled those identified as differentially expressed by strain. Metabolite analyses revealed that the components of the glutathione antioxidant pathway were different between strains, specifically in the formation of mixed disulfides. Additionally, selenium metabolites such as selenohomocystiene and selenocystathionine were similarly differentially expressed. Transcriptomic analysis revealed similar findings, as evidenced by differences in glutathione peroxidase, peroxiredoxin, and the inflammatory transcription factors RelA and Jun. In summary, an multi-omics integrated approach identified that murine strain disproportionately impacts baseline expression of antioxidant systems in lung tissues. We speculate that strain-dependent differences contribute to discrepant pulmonary responses in preclincal mouse models, with deleterious effects on clinical translation.

Effects of ketamine, propofol, or thiopental administration on intraocular pressure and qualities of induction of and recovery from anesthesia in horses.

OBJECTIVE: To assess the effects of ketamine hydrochloride, propofol, or compounded thiopental sodium administration on intraocular pressure (IOP) and qualities of induction of and recovery from anesthesia in horses. ANIMALS: 6 healthy adult horses. PROCEDURES: Horses were sedated with xylazine hydrochloride (0.5 mg/kg), and anesthesia was induced with guaifenesin followed by ketamine (2 mg/kg), propofol (3 mg/kg), or thiopental (4 mg/kg) in a crossover study with ≥ 1 week between treatments. For each horse, IOP in the right eye was measured with a handheld applanation tonometer before and after xylazine administration, at the time of recumbency, and every 3 minutes after induction of anesthesia until spontaneous movement was observed. Cardiorespiratory responses and venous blood measurements were recorded during anesthesia. Induction of and recovery from anesthesia were subjectively evaluated by investigators who were unaware of the anesthetic treatment of each horse. Data were analyzed via a repeated-measures ANOVA with Holm-Sidák post hoc comparisons. RESULTS: Compared with findings after xylazine administration (mean ± SD, 17 ± 3 mm Hg), thiopental decreased IOP by 4 ± 23%, whereas propofol and ketamine increased IOP by 8 ± 11% and 37 ± 16%, respectively. Compared with the effects of ketamine, propofol and thiopental resulted in significantly lower IOP at the time of recumbency and higher heart rates at 3 minutes after induction of anesthesia. No other significant differences among treatments were found. CONCLUSIONS AND CLINICAL RELEVANCE: These findings support the use of thiopental or propofol in preference to ketamine for horses in which increases in IOP should be minimized.