부산대학교 도서관

ABSTRACT: Sepsis is the most frequent risk factor for acute kidney injury (AKI) in critically ill infants. Sepsis-induced dysregulation of kidney microcirculation in newborns is unresolved. The objective of this study was to use the translational swine model to evaluate changes in kidney function during the early phase of sepsis in newborns and the impact of fluid plus norepinephrine (NE) resuscitation. Newborn pigs (3-7-day-old) were allocated randomly to three groups: 1) Sham, 2) Sepsis (cecal ligation and puncture; CLP) without subsequent resuscitation, and 3) Sepsis with Lactated Ringer plus NE resuscitation. All animals underwent standard anesthesia and mechanical ventilation. Cardiac output (COP) and glomerular filtration rate (GFR) were measured non-invasively. Mean arterial pressure (MAP), total renal blood flow (RBF), cortical perfusion (coPf), medullary perfusion (mePf), and medullary tissue oxygen tension (mtPO2) were determined for 12 h. CLP decreased MAP and COP by more than 50%, with a proportional increase in renal vascular resistance (RVR) and a 60-80% reduction in RBF, coPf, mePf, and mtPO2 compared to sham. CLP also decreased GFR by ~79% and increased AKI biomarkers. Isolated foci of tubular necrosis were observed in the septic piglets. Except for mtPO2, changes in all these parameters were ameliorated in resuscitated piglets. Resuscitation also attenuated sepsis-induced increases in the levels of plasma C-reactive protein, proinflammatory cytokines, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, and renal NLRP3 inflammasome. These data suggest that newborn pigs subjected to CLP develop hypodynamic septic AKI. Early implementation of resuscitation lessens the degree of inflammation, AKI, and liver injury.