Reversal of cerebral ischaemia and hypoxia and of sickness behaviour by megadose sodium ascorbate in ovine Gram-negative sepsis.

Background: The mechanisms by which megadose sodium ascorbate improves clinical status in experimental sepsis is unclear. We determined its effects on cerebral perfusion, oxygenation, and temperature, and plasma levels of inflammatory biomarkers, nitrates, nitrites, and ascorbate in ovine Gram-negative sepsis.

Methods: Sepsis was induced by i.

Effects of furosemide, acetazolamide and amiloride on renal cortical and medullary tissue oxygenation in non-anaesthetised healthy sheep.

It has been proposed that diuretics can improve renal tissue oxygenation through inhibition of tubular sodium reabsorption and reduced metabolic demand. However, the impact of clinically used diuretic drugs on the renal cortical and medullary microcirculation is unclear. Therefore, we examined the effects of three commonly used diuretics, at clinically relevant doses, on renal cortical and medullary perfusion and oxygenation in non-anaesthetised healthy sheep.

Renal arterial infusion of tempol prevents medullary hypoperfusion, hypoxia, and acute kidney injury in ovine Gram-negative sepsis.

Aim: Renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI) in ovine sepsis. Oxidative/nitrosative stress, inflammation, and impaired nitric oxide generation may contribute to such pathophysiology. We tested whether the antioxidant and anti-inflammatory drug, tempol, may modify these responses.

Splanchnic sympathetic nerve denervation improves bacterial clearance and clinical recovery in established ovine Gram-negative bacteremia.

Background: The autonomic nervous system can modulate the innate immune responses to bacterial infections via the splanchnic sympathetic nerves. Here, we aimed to determine the effects of bilateral splanchnic sympathetic nerve denervation on blood pressure, plasma cytokines, blood bacterial counts and the clinical state in sheep with established bacteremia.

Methods: Conscious Merino ewes received an intravenous infusion of Escherichia coli for 30 h (1 × 10 colony forming units/mL/h) to induce bacteremia.

Associations Between Systemic and Cerebral Inflammation in an Ovine Model of Cardiopulmonary Bypass.

Background: Intraoperative inflammation may contribute to postoperative neurocognitive disorders after cardiac surgery requiring cardiopulmonary bypass (CPB). However, the relative contributions of general anesthesia (GA), surgical site injury, and CPB are unclear.

Methods: In adult female sheep, we investigated (1) the temporal profile of proinflammatory and anti-inflammatory cytokines and (2) the extent of microglia activation across major cerebral cortical regions during GA and surgical trauma with and without CPB (N = 5/group).

Rapid and persistent decrease in brain tissue oxygenation in ovine gram-negative sepsis.

The changes in brain perfusion and oxygenation in critical illness, which are thought to contribute to brain dysfunction, are unclear due to the lack of methods to measure these variables. We have developed a technique to chronically measure cerebral tissue perfusion and oxygen tension in unanesthetized sheep. Using this technique, we have determined the changes in cerebral perfusion and Po during the development of ovine sepsis.

Urinary and renal oxygenation during dexmedetomidine infusion in critically ill adults with mechanistic insights from an ovine model.

Purpose: Examine effects of dexmedetomidine on bladder urinary oxygen tension (PuO) in critically ill patients and delineate mechanisms in an ovine model.

Materials And Methods: In 12 critically ill patients: oxygen-sensing probe inserted in the bladder catheter and dexmedetomidine infusion at a mean (SD) rate of 0.9 ± 0.

Reversal of the Pathophysiological Responses to Gram-Negative Sepsis by Megadose Vitamin C.

Objectives: Oxidative stress appears to initiate organ failure in sepsis, justifying treatment with antioxidants such as vitamin C at megadoses. We have therefore investigated the safety and efficacy of megadose sodium ascorbate in sepsis.

Design: Interventional study.