Hospital for Small Animals, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK; The Queen's Medical Research Institute, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Hospital for Small Animals, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
Domest Anim Endocrinol. 2020 Jul;72:106437. doi: 10.1016/j.domaniend.2020.106437. Epub 2020 Jan 23.
Critical illness due to sepsis is a major global health concern associated with a high burden of mortality and cost. Glucocorticoid dysregulation in human sepsis is associated with poorer outcomes. This study examines glucocorticoid metabolism in septic canine patients to delineate elements of cellular dysregulation in common with critically ill humans and explore potential differences. This was a prospective case-control study conducted in the veterinary specialist critical care departments of two University teaching hospitals. Critically ill canine patients with naturally occurring sepsis or septic shock were compared with an in-hospital control population. Serum total, bound, and free cortisol concentrations were increased in septic shock (P < 0.001), and higher bound cortisol was associated with nonsurvival (P = 0.026). Urinary Gas Chromatography-Tandem Mass Spectrometry was performed to assess urinary glucocorticoid metabolites and estimate intracellular glucocorticoid metabolism. Decreased renal 11β-hydroxysteroid dehydrogenase 2 (11βHSD2) activity inferred from increased urinary cortisol-to-cortisone ratio was observed in critically ill dogs (P < 0.001). Decreased 11βHSD2 activity (P = 0.019) and increased A-ring reduction of cortisone (P = 0.001) were associated with nonsurvival within the critically ill dogs. Intriguingly, two dogs were identified with low circulating total cortisol (<2 mg/dL) associated with increased A-ring reduction of cortisol, not previously described. Investigation of spontaneous canine sepsis and septic shock reveals dysregulation of cortisol to cortisone conversion similar to that observed in human patients, but with differences in A-ring reduction compared with those reported in humans. In addition, two dogs with high levels of cortisol inactivation associated with low circulating cortisol concentrations were identified.
脓毒症导致的危重病是一个全球性的重大健康问题，与高死亡率和高医疗费用负担有关。人类脓毒症中糖皮质激素失调与预后较差有关。本研究检测了脓毒症犬的糖皮质激素代谢，以阐明与重症患者共有的细胞失调因素，并探讨潜在的差异。这是一项在两所大学教学医院的兽医专科重症监护病房进行的前瞻性病例对照研究。将患有自然发生的脓毒症或感染性休克的危重病犬与院内对照人群进行比较。脓毒症性休克患者的血清总、结合和游离皮质醇浓度升高（P < 0.001），结合皮质醇升高与非生存相关（P = 0.026）。进行尿气相色谱-串联质谱分析，以评估尿糖皮质激素代谢产物并估计细胞内糖皮质激素代谢。从尿皮质醇/皮质酮比值升高推断出，危重病犬的肾脏 11β-羟类固醇脱氢酶 2（11βHSD2）活性降低（P < 0.001）。11βHSD2 活性降低（P = 0.019）和皮质酮 A 环还原增加（P = 0.001）与危重病犬的非生存相关。有趣的是，有两只狗的循环总皮质醇（<2 mg/dL）低，但皮质醇的 A 环还原增加，这与以前的描述不同。自发性犬脓毒症和感染性休克的研究表明，皮质醇向皮质酮的转化失调与人类患者观察到的相似，但 A 环还原与人类报道的不同。此外，还发现了两只狗的皮质醇失活水平高，但循环皮质醇浓度低，这与以前的描述不同。
