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Acute kidney injury (AKI) in critically ill patients is a devastating illness associated with prolonged hospital stay and high mortality. Limited progress has been made in the field of AKI, and its treatment using renal replacement therapy, at best, only provides partial renal support. Ischemia-reperfusion rodent AKI models do not resemble human renal(More)
The effect of extracorporeal blood purification on clinical outcomes in sepsis is assumed to be related to modulation of plasma cytokine concentrations. To test this hypothesis directly, we treated rats that had a cecal ligation followed by puncture (a standard model of sepsis) with a modest dose of extracorporeal blood purification that did not result in(More)
OBJECTIVE To compare the acute effects of 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis. DESIGN Controlled laboratory experiment. SETTING University laboratory. SUBJECTS Sixty adult, male Sprague-Dawley rats. INTERVENTIONS We induced sepsis by cecal ligation and puncture and randomized animals to(More)
OBJECTIVE To explore the relationships among bactericidal antimicrobial treatment of sepsis, inflammatory response, severity of acute kidney injury, and outcomes. DESIGN Controlled laboratory experiment. SETTING University laboratory. INTERVENTIONS Sepsis was induced by cecal ligation and puncture in 52 rats and was treated with either bactericidal(More)
INTRODUCTION Promising preclinical results have been obtained with blood purification therapies as adjuvant treatment for sepsis. However, the mechanisms by which these therapies exert beneficial effects remain unclear. Some investigators have suggested that removal of activated leukocytes from the circulation might help ameliorate remote organ injury. We(More)
A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of(More)
BACKGROUND In most patients, acute kidney injury (AKI) represents the combined effects of ischemic, toxic and inflammatory insults. No effective pharmacologic interventions have been developed to prevent AKI or to improve outcomes to date. Cyclosporine A (CsA) is a calcineurin inhibitor that mediates T-cell receptor signaling, suppresses inflammatory(More)
OBJECTIVES Although blood purification improves outcomes in animal studies of sepsis, results of clinical trials have been mixed. We conducted a systematic review and meta-analysis of randomized trials to determine the association between various blood purification techniques and all-cause mortality in humans with sepsis. DATA SOURCES We searched for(More)
To determine the dose-response effects of noradrenaline on the systemic and renal circulations during septic shock. Prospective controlled experiment in a university animal laboratory. Eight anaesthetized dogs. Transonic flow probes were surgically placed on the aorta via a left lateral thoracotomy and on the left renal artery. Blood pressure was measured(More)