Effects of sodium-glucose transporter-2 inhibition on systemic hemodynamics, renal function, and intra-renal oxygenation in sepsis-associated acute kidney injury.

Background: People with type 2 diabetes mellitus treated with sodium-glucose transporter-2 inhibitors (SGLT2i) have lower rates of acute kidney injury (AKI). Sepsis is responsible for the majority of AKI in critically ill patients. This study investigated whether SGLT2i is renoprotective in an ovine model of Gram-negative septic AKI.

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.

Differential responses of cerebral and renal oxygenation to altered perfusion conditions during experimental cardiopulmonary bypass in sheep.

We tested whether the brain and kidney respond differently to cardiopulmonary bypass (CPB) and to changes in perfusion conditions during CPB. Therefore, in ovine CPB, we assessed regional cerebral oxygen saturation (rSO ) by near-infrared spectroscopy and renal cortical and medullary tissue oxygen tension (PO ), and, in some protocols, brain tissue PO , by phosphorescence lifetime oximetry. During CPB, rSO correlated with mixed venous SO (r = 0.

Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial.

Background: Mega-dose sodium ascorbate (NaAscorbate) appears beneficial in experimental sepsis. However, its physiological effects in patients with septic shock are unknown.

Methods: We conducted a pilot, single-dose, double-blind, randomized controlled trial.

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).

The effects of recruitment of renal functional reserve on renal cortical and medullary oxygenation in non-anesthetized sheep.

Aim: Recruitment of renal functional reserve (RFR) with amino acid loading increases renal blood flow and glomerular filtration rate. However, its effects on renal cortical and medullary oxygenation have not been determined. Accordingly, we tested the effects of recruitment of RFR on renal cortical and medullary oxygenation in non-anesthetized sheep.

Continuous bladder urinary oxygen tension as a new tool to monitor medullary oxygenation in the critically ill.

Acute kidney injury (AKI) is common in the critically ill. Inadequate renal medullary tissue oxygenation has been linked to its pathogenesis. Moreover, renal medullary tissue hypoxia can be detected before biochemical evidence of AKI in large mammalian models of critical illness.

Effects of changes in inspired oxygen fraction on urinary oxygen tension measurements.

Background: Continuous measurement of urinary PO (PuO) is being applied to indirectly monitor renal medullary PO. However, when applied to critically ill patients with shock, its measurement may be affected by changes in FiO and PaO and potential associated O diffusion between urine and ureteric or bladder tissue. We aimed to investigate PuO measurements in septic shock patients with a fiberoptic luminescence optode inserted into the urinary catheter lumen in relation to episodes of FiO change.

Influence of moderate hypothermia on renal and cerebral haemodynamics and oxygenation during experimental cardiopulmonary bypass in sheep.

Aim: Cardiac surgery requiring cardiopulmonary bypass (CPB) can result in renal and cerebral injury. Intraoperative tissue hypoxia could contribute to such organ injury. Hypothermia, however, may alleviate organ hypoxia.

Update on vitamin C administration in critical illness.

Purpose Of Review: Several studies have recently explored the effects of intravenous vitamin C in sepsis. We aimed to summarize their findings to provide perspectives for future research.

Recent Findings: Sepsis trials examined 6 g/day of intravenous vitamin C with or without the thiamine and/or hydrocortisone compared with placebo or hydrocortisone.

Role of perioperative hypotension in postoperative acute kidney injury: a narrative review.

Perioperative hypotension is common and associated with poor outcomes, including acute kidney injury (AKI). The mechanistic link between perioperative hypotension and AKI is at least partly a consequence of the susceptibility of the kidney, and particularly the renal medulla, to ischaemia and hypoxia. Several critical gaps in our knowledge lead to uncertainty about when and how to intervene to prevent AKI attributable to perioperative hypotension.

Renal and Cerebral Hypoxia and Inflammation During Cardiopulmonary Bypass.

Cardiac surgery-associated acute kidney injury and brain injury remain common despite ongoing efforts to improve both the equipment and procedures deployed during cardiopulmonary bypass (CPB). The pathophysiology of injury of the kidney and brain during CPB is not completely understood. Nevertheless, renal (particularly in the medulla) and cerebral hypoxia and inflammation likely play critical roles.

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.

Targeting Oxidative Stress in Septic Acute Kidney Injury: From Theory to Practice.

Sepsis is the leading cause of acute kidney injury (AKI) and leads to increased morbidity and mortality in intensive care units. Current treatments for septic AKI are largely supportive and are not targeted towards its pathophysiology. Sepsis is commonly characterized by systemic inflammation and increased production of reactive oxygen species (ROS), particularly superoxide.

Renal, Cardiac, and Autonomic Effects of Catheter-Based Renal Denervation in Ovine Heart Failure.

[Figure: see text].