EFFECT OF PRETREATMENT WITH HEME-BASED SOLUTIONS ON LIVER MICROCIRCULATION AFTER HEMORRHAGIC SHOCK

Abstract

Pretreatment with hemoglobin-based oxygen carriers (diaspirin-crosslinked hemoglobin, DCLHb; hemoglobin glutamer-200, HbG) induces heme oxygenase-1 (HO-1), but increases organ dysfunction and mortality in a rat model of hemorrhagic shock. In contrast, pretreatment with the non oxygen-carrying hemin arginate (HAR) reduces shock-induced organ failure and mortality probably through HO-1 induction. The NO-scavenging and vasoconstrictive effects of free hemoglobin may affect microcirculation after shock. Aim of the study was to assess the effect of pretreatment with DCLHb, HbG or HAR on liver microcirculation. 24 h after pretreatment with DCLHb (1 g/kg), HbG (1 g/kg) or HAR (5 mg/kg) rats were subjected to 1 h hemorrhage (MAP: 35 ± 5 mmHg)/2 h resuscitation. Liver microcirculation was ssessed by intravital microscopy. Animals treated with Ringer's solution served as controls (vehicle). DCLHb, HbG, and HAR induced HO-1 in the liver. However, DCLHb and HbG-pretreatment did not improve sinusoidal perfusion and increased NAD(P)H autofluorescence in liver tissue similar to vehicle-treated animals. In contrast, HAR-pretreatment significantly improved sinusoidal perfusion. Blockade of the HO-pathway by SnMP-IX (10 μmol/kg) after HAR-pretreatment abolished the protective effects. Although DCLHb, HbG, and HAR induce HO-1 only HAR-pretreatment improves liver microcirculation. The induction of HO-1 expression and the lack of NO-scavenging through HAR may play an important role in preventing shock-induced sinusoidal perfusion failure.