Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial

Abstract

A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.

High mobility group box protein 1 neutralization therapy in ovine bacteremia: Lessons learned from an ovine septic shock model incorporating intensive care support

“…Characteristics of study sheep and outcomes are depicted in Table III. Initially, two sheep (#1 and #2) were administered the same E. coli dose as used in previous studies (1×10 8 CFU/kg) (15,16), however the sheep required little NorA and did not progress to prolonged septic shock. To replicate a degree of sickness severity observed in previous studies, an increased E. coli dose (1.5×10 8 CFU/kg) was employed for the remaining sheep within the study (#3–6).…”

“…Border Leicester × Merino ewes (2.4–4 years old) were group housed at The South Australian Health and Medical Research Institute and given free access to food and water. A model of OSSICS was performed on six sheep previously published protocols (15,16). Briefly, anesthesia was induced in overnight fasted randomly selected sheep by intravenous (IV) injection of Thiopentone (15 mg/kg) before intubation and ventilation with isoflurane (2%) in oxygen the morning following fasting (8–10 am).…”

“…The inoculum (1 ml/kg) was administered to prepared, anaesthetized sheep as an IV infusion in the over one hour to achieve 1–1.5×10 8 CFU/kg based on previous studies (15,16). Anti-HMGB1 antibodies (10 mg/kg) were administered via IV infusion over one hour commencing two hours after the induction of sepsis.…”

“…Instrumented septic ovine models have been used to study acute lung injury (11), fluid resuscitation (12) and renal inflammation (13). Recently, an ovine septic shock incorporating intensive care supports (OSSICS) model which recapitulates multiple pathophysiological hallmarks of human septic shock (14) has been used to investigate renal pathology (15) and thyroid hormone therapy (16) in sepsis. However, the utility of this model for studying the physiologic effects of immunomodulatory therapies has not been established.…”

Venous blood for the analysis of acid–base status in a model of septic shock

“…This was a post‐hoc study of data obtained from previously published studies of a septic shock model 4 . The project was approved by the institution's animal ethics committee.…”