EFFECTS OF DIASPIRIN-CROSS-LINKED HEMOGLOBIN (DCLHB(TM)) ON THE MICROCIRCULATION OF STRIATED SKIN MUSCLE IN THE HAMSTER - A STUDY ON SAFETYAND TOXICITY

Hemoglobin-based oxygen-carrying solutions are reported to exert vasoc onstrictor effects and to enhance oxygen radical formation, particular ly during ischemia-reperfusion. This study investigates whether diaspi rin-cross-linked hemoglobin (DCLHb(TM)) affects the microvascular inte grity of striated skin muscle. The microcirculation model in the hamst er and intravital fluorescence microscopy were applied for investigati on 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-lastin g (0 to 2 minutes) arteriolar constriction (similar to 20% reduction i n baseline diameter), (2) significantly influenced arteriolar vasomoti on, (3) increased venular red blood cell velocity by 1.5-fold (p < 0.0 5 vs dextran, M-r 60,000), and (LL) did not enhance microvascular leuk ocyte-endothelium interaction or endothelial permeability. Resuscitati on 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 pa rameters 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 si gnificantly enhanced after resuscitation with AuB and Dx-60, whereas t his phenomenon was absent after DCLHb(TM). These data demonstrate that DCLHb(TM) increases venular red blood cell velocity under both nonisc hemic and postischemic conditions without inducing enhanced leukocyte- endothelium interaction in the microcirculation of striated skin muscl e.