Effects of diaspirin-cross-linked hemoglobin (DCLHb TM) on the microcirculation of striated skin muscle in the hamster: A study on safety and toxicity

Abstract

Hemoglobin-based oxygen-carrying solutions are reported to exert vasoconstrictor effects and to enhance oxygen radical formation, particularly during ischemiareperfusion. This study investigates whether diaspirin-cross-linked hemoglobin (DCLHb TM) affects the microvascular integrity of striated skin muscle. The microcirculation model in the hamster and intravital fluorescence microscopy were applied for investigation of the microvascular changes in striated skin muscle. Hypervolemic infusion (500 mg · kg −1, iv) and isovolemic exchange transfusion (3.3 gm · kg −1 IV; hematocrit 30%) with DCLHb TM (1) led to a short-lasting (0 to 2 minutes) arteriolar constriction (~20% reduction in baseline diameter), (2) significantly influenced arteriolar vasomotion, (3) increased venular red blood cell velocity by 1.5-fold ( p < 0.05 vs dextran, M r, 60,000), and (4) did not enhance microvascular leukocyteendothelium interaction or endothelial permeability. Resuscitation from severe hemorrhagic shock with autologous blood (AuB) or DCLHb TM (33 ml · kg −1, iv) immediately restored mean arterial pressure and heart rate, whereas 6% dextran (60 kd)(Dx-60) did not return these parameters to baseline. Venular red blood cell velocity was restored to 110% of baseline after DCLHb TM, to 90% of baseline after AuB, and to 45% of baseline after Dx-60. Leukocyte-endothelium interaction was significantly enhanced after resuscitation with AuB and Dx-60, whereas this phenomenon was absent after DCLHbTM. These data demonstrate that DCLHbTM increases venular red blood cell velocity under both nonischemic and postischemic conditions without inducing enhanced leukocyte-endothelium interaction in the microcirculation of striated skin muscle.