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, Methods: Anesthetized and ventilated rats (n=44) were subjected to an endotoxemic shock following lipopolysaccharide (LPS) infusion. CµPO2 was measured in exposed kidneys using a phosphorescence-quenching method. Rats were randomly assigned to 5 groups: (1) unresuscitated LPS, (2) ringer's acetate (LPS+RA), PO2 (CµPO2) and skeletal microcirculatory flow thereby limiting sepsis-induced acute kidney injury (AKI) in a rat model of endotoxemia
, ) LPS+RA+PEGHbCO (320mg.kg -1 )
, and myeloperoxidase-stained leukocytes in glomerulus and peritubular areas were analyzed. Sepsis-induced histological damages were assessed. Finally, plasma levels of IL-6, heme oxygenase-1, malondialdehyde, and syndecan-1 were assessed by ELISA. Results: CµPO2 was higher in groups resuscitated with PEGHbCO, 36±6 mmHg (mean diff, p.95
, PEGHbCO, reduced the number of non-flowing, intermittent or sluggish capillaries compared to resuscitation with RA alone (P<0.05) while increasing the number of normally perfused vessels (P<0.05). Sepsis-induced kidney immunohistochemistry and histological alterations were not mitigated by PEGHbCO 1h after resuscitation. Renal leukocyte infiltration and plasma levels of IL-6, heme oxygenase-1, malondialdehyde, and syndecan-1 were similar across groups, P=0.023), for LPS+RA+PEGHbCO and LPS+RA+PEGHbCO+NE respectively, compared to 23±12mmHg for LPS+RA
, PEGylated carboxyhemoglobin, carbon monoxide, hemoglobin-based oxygen carrier, renal injury, sepsis Chapter 11 excluded any interference between Palladium(II)-meso-tetra(4-carboxyphenyl)-porphyrin (Pd-TCCP) and PEGHbCO (in vitro) prior to the in vivo experiment. Kidney function Plasma creatinine and urine creatinine were measured using an automatic analyzer, Keywords: acute kidney injury, p.702
We established a calibration curve for creatinine levels prior to measurements to correct for a significant interference due to the presence of PEGylated-carboxyhemoglobin. The glomerular filtration rate was estimated at the end of the experiment using the measurement of creatinine clearance (Clcrea): Clcrea=(UCrea x V)/(time x PCrea) where UCrea is the concentration of creatinine in urine (mmol.l-1), V is the urine volume (ml) per unit time of urine collection and PCrea is the concentration of creatinine in plasma (mmol.l-1). The renal oxygen delivery (DO2) and consumption (VO2hand-held in vivo microscope using incident dark-field (IDF) imaging, CytoCam? (Braedius Scientific ,
, Central Venous Pressure, NE: norepinephrine. Repeated measures 2-way ANOVA test used with Bonferroni's correction to adjust for multiple comparisons. * adjusted P<0.01 vs, MAP: Mean Arterial Pressure, RBF: Renal Blood Flow
, LPS+RA+PEGHbCO+NE groups but not in the LPS+RA group
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