Effect of polyethylene-glycolated carboxyhemoglobin on renal microcirculation in a rat model of hemorrhagic shock

Abstract

Background: Primary resuscitation fluid to treat hemorrhagic shock remains controversial. Use of hydroxyethyl starches raised concerns of acute kidney injury. Polyethylene-glycolated carboxyhemoglobin, which has carbon monoxide-releasing molecules and oxygen-carrying properties, was hypothesized to sustain cortical renal microcirculatory Po2 after hemorrhagic shock and reduce kidney injury. Methods: Anesthetized and ventilated rats (n = 42) were subjected to pressure-controlled hemorrhagic shock for 1 h. Renal cortical Po2 was measured in exposed kidneys using a phosphorescence quenching method. Rats were randomly assigned to six groups: polyethylene-glycolated carboxyhemoglobin 320 mg · kg-1, 6% hydroxyethyl starch (130/0.4) in Ringer's acetate, blood retransfusion, diluted blood retransfusion (∼4 g · dl-1), nonresuscitated animals, and time control. Nitric oxide and heme oxygenase 1 levels were determined in plasma. Kidney immunohistochemistry (histologic scores of neutrophil gelatinase-Associated lipocalin and tumor necrosis factor-) and tubular histologic damages analyses were performed. Results: Blood and diluted blood restored renal Po2 to 51 ± 5 mmHg (mean difference,-18; 95% CI,-26 to-11; P < 0.0001) and 47 ± 5 mmHg (mean difference,-23; 95% CI,-31 to-15; P < 0.0001), respectively, compared with 29 ± 8 mmHg for hydroxyethyl starch. No differences between polyethylene-glycolated carboxyhemoglobin and hydroxyethyl starch were observed (33 ± 7 mmHg vs. 29 ± 8 mmHg; mean difference,-5; 95% CI,-12 to 3; P = 0.387), but significantly less volume was administered (4.5 [3.3-6.2] vs. 8.5[7.7-11.4] ml; mean rank difference, 11.98; P = 0.387). Blood and diluted blood increased the plasma bioavailability of nitric oxide compared with hydroxyethyl starch (mean rank difference,-20.97; P = 0.004; and-17.13; P = 0.029, respectively). No changes in heme oxygenase 1 levels were observed. Polyethylene-glycolated carboxyhemoglobin limited tubular histologic damages compared with hydroxyethyl starch (mean rank difference, 60.12; P = 0.0012) with reduced neutrophil gelatinase-Associated lipocalin (mean rank difference, 84.43; P < 0.0001) and tumor necrosis factor- (mean rank difference, 49.67; P = 0.026) histologic scores. Conclusions: Polyethylene-glycolated carboxyhemoglobin resuscitation did not improve renal Po2 but limited tubular histologic damages and neutrophil gelatinase-Associated lipocalin upregulation after hemorrhage compared with hydroxyethyl starch, whereas a lower volume was required to sustain macrocirculation.