Since the beginning of this century, the development of
hemoglobin based
oxygen carriers has been propagated for replacement of the
oxygen carrying properties of red blood cells. A breakthrough has been impeded by problems related to the
hemoglobin molecule itself and the ingredients of the
solution, resulting in nephrotoxic side effects, limited intravascular half-life,
vasoconstrictor potential and potential catalysis of
oxygen free radical formation. Using intravital fluorescence microscopy and the dorsal skin fold chamber model of the awake Syrian golden hamster, the microcirculatory changes occurring in the thin striated skin muscle were quantitatively analyzed before and after administration of an ultrapurified
polymerized bovine hemoglobin solution (U-PBHb) under the following experimental conditions: (1) Hypervolemic infusion of U-PBHb at approximately 10% of calculated blood volume, (2) isovolemic exchange transfusion with U-PBHBb by replacing approximately 50% of calculated blood volume and (3) severe
hemorrhagic shock by acute
bleeding of approximately 50% of calculated blood volume to a MAP of 35 +/- 5 mm Hg for 45 min followed by
resuscitation with U-PBHb. Control animals received equivalent treatment with vehicle
solution,
dextran 60 (M(r) 60,000 D) or
Ringer's lactate. The microcirculation was found unchanged after both hypervolemic infusion and isovolemic exchange transfusion with respect to perfusion quality and leukocyte/ endothelium interaction while a decrease of functional capillary density by approximately 25% was observed after exchange transfusion with U-PBHb. After
hemorrhagic shock, microvascular perfusion was most efficiently restored by U-PBHb without evidence of arteriolar vasoconstriction or activation of leukocyte/endothelial cell interactions during reperfusion. These data indicate, the U-PBHb exerts no unwanted side effects on the microcirculation either under non-ischemic or post-ischemic conditions. The microcirculatory findings post-
resuscitation let U-PBHb appear as a safe
resuscitation fluid which is superior to the commonly used
resuscitation fluids,
Ringer's lactate and
dextran 60.