Duspirin Crosslinked Hemoglobin (Dclhb^™): More Effective Than Lactated Ringer's Solution in Restoring Central Venous Oxygen Saturation After Hemorrhagic Shock in Rats

Abstract

Central venous oxygen saturation (ScvO2) has been shown to reflect tissue oxygen consumption in hemorrhagic shock. The purpose of this study was to test whether the "blood substitute" diaspirin crosslinked hemoglobin (DCLHb, Baxter Healthcare, Round Lake, IL) might be more effective than lactated Ringer's solution (LR) at restoring tissue oxygenation, as measured by ScvO2, when used as a resuscitative fluid following hemorrhage. Conscious male Sprague-Dawley rats (250-350 gm) were bled through a jugular venous catheter to a target central venous base deficit of 15 +/- 2 mmol/L. Animals were immediately resuscitated with either 10% DCLHb (1:1) or LR (3:1), based on shed blood volume, followed by a maintenance infusion of LR until completion of the experiment. Central venous blood was sampled at baseline, prior to resuscitation and every 15 minutes for the first hour following resuscitation. While the baseline and pre-resuscitation ScvO2 values were not significantly different between groups, ScvO2 values were greater (P < or = 0.01) in the DCLHb group at all times following resuscitation. Furthermore, DCLHb restored SvO2 to baseline by 15 minutes after resuscitation, whereas LR resuscitation never restored ScvO2 to baseline. Since venous desaturation is one of the major compensatory mechanisms by which oxygen consumption is maintained under conditions of limited oxygen supply, these data suggest that animals resuscitated with DCLHb had a more rapid restoration of tissue oxygenation than those resuscitated with LR in this model of hemorrhagic shock.

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some PhysiologyBlut ist ein ganz besondrer Saft

“…Investigation of the pressor effect's mechanism indicated that this response is most likely multifactorial (section IV.H). Improved tissue oxygenation and reversal of base deficit by DCLHb solutions was demonstrated in a range of circumstances. ,,,,,− Efficacy as a resuscitation fluid was reported in various hemorrhagic shock models. ,,− ,,,,,,,− ,1251a Improved survival was reported in septic rats treated with DCLHb . Redistribution of blood flow to vital organs was observed. ,,,1251a Attenuation of postischemic reperfusion injury in skin muscle has been reported .…”

Untitled

“…In this respect attention must be paid to the recent development of hemorrhagic shock models with a target endpoint of metabolic acidosis [ 52 - 54 ]. Schultz [ 52 ] and Powell [ 53 ] and their groups studied bacterial translocation and restoration of central venous oxygen saturation after BD-guided hemorrhagic shock in rats. Also, DeAngeles and coworkers [ 54 ] studied resuscitation from BD/lactate guided hemorrhagic shock with diaspirin cross-linked hemoglobin, blood, and hetastarch in sheep.…”

&alpha;&alpha;&ndash;Crosslinked Hemoglobin: Was Failure Predicted by Preclinical Testing?

“…A later study, using a more aggressive hemorrhage (70% of blood volume), also showed better return of blood pressure and heart rate in the animals given DCLHb compared to blood [86]. Further studies showing efficacy of DCLHb in resuscitation of hemorrhaged rats included measurements of GI mucosal oxygen tension [145], base deficit [146]and subcutaneous oxygen tension [147, 148]central venous oxygen saturation [149], as well as use in a burn model [150], all suggested efficacy for DCLHb.…”