Rekombinantes humanes Hämoglobin rHb2.0 erlaubt Hämodilution ohne Beeinträchtigung der Mikrozirkulation
Introduction: Infusion of stroma-free hemoglobin preparations causes arteriolar vasoconstriction and capillary perfusion deficit. Scavenging of NO is perceived as a key factor, but cannot be eliminated by crosslinking or polymerization of hemoglobin. Recombinant technology allows for specific steric modifications of the hemoglobin molecule itself. The novel formulation rHb2.0 is based on a genetically modified human hemoglobin molecule and provides reduced NO-scavenging capacity. Here, we present the first data on the effect of rHb2.0 on macro- and microcirculation. Material and Methods: Awake Syrian golden hamsters fitted with dorsal skinfold chambers were hemodiluted to a hematocrit of 30% with either Dextran 60 (Medisan, Uppsala, Sweden), rHbl.l (normal NO-scavenging capacity; Baxter Healthcare Corp., Boulder, Colo., USA) or rHb2.0 (reduced NO-scavenging capacity; Baxter Healthcare Corp.) (n = 7 in each group). Arteriolar and venular diameter, venular red blood cell velocity, functional capillary density and leukocyte-endothelium interaction were determined by intravital fluorescence microscopy; in addition, macrohemodynamics and blood gases were assessed. Values are given as mean ± SD. Friedman ANOVA and Dunnett’s test were used for multiple comparisons vs baseline, α was set to 5%. Results: In comparison to hemodilution with dextran, rHbl.l elicited an increase of mean arterial blood pressure, a reduction of FCD and enhanced leukocyte-endothelium interaction. These changes were absent when rHb2.0 was used for isovolemic hemodilution. Conclusion: The novel recombinant hemoglobin solution rHb2.0 with reduced NO-scavenging capacity is void of vasopressor activity in our model and does not compromise the microcirculation. In this respect, it appears as a suitable oxygen carrier for volume replacement.
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