Effects of Ultra-Purified Polymerized Bovine Hemoglobin on Local Tissue Oxygen Tension in Striated Skin Muscle – An Efficacy Study in the Hamster

Abstract

The development of hemoglobin-based oxygen carriers has been propagated for replacement of the oxygen carrying properties of red blood cells for almost one century. Using a Clark-type multi-wire oxygen surface electrode and the dorsal skin fold chamber model of the awake Syrian golden hamster, local tissue pO₂ was analyzed in the thin striated skin muscle before and after administration of an ultrapurified polymerized bovine hemoglobin solution (U-PBHb^®, Biopure Corp., Boston, Mass., USA) under the following experimental conditions: (a) hypervolemic infusion with U-PBHb at ∼10% of calculated blood volume, and (b) isovolemic exchange transfusion with U-PBHb by replacing ∼50% of calculated blood volume. Control animals of group a received equivalent treatment with either isotonic saline or dextran 60, control animals of group b received dextran 60. Local tissue pO₂ was found slightly decreased after both hypervolemic infusion and isovolemic exchange transfusion with U-PBHb, while frequency distribution curves of local tissue pO₂ were found more narrow (less values <10 mm Hg and >25 mm Hg), suggesting a more homogeneous tissue pO₂ distribution. The data thus indicate that U-PBHb slightly decreases mean tissue pO₂ after both hypervolemic infusion and isovolemic exchange transfusion which is accompanied by an effective homogenization of local tissue pO₂ distribution as compared to dextran 60.

Blood Substitutes

“…The infusion of HBOC consistently effected a sustained stabilization of hemodynamics and tissue oxygenation and significantly decreased mortality [35,64,90,103]. Moreover, the postischemic interaction between leukocytes and the endothelium could be attenuated by infusion of HBOCs based on human [42,79] as well as bovine Hb [6].…”

Moderate Hemodilution with rHb2.0 for Injection

“…Our laboratory has investigated several different hemoglobin solutions with respect to their effects on the microcirculation in the dorsal skinfold chamber after moderate ANH, including polymerized bovine hemoglobin (U-PBHb) [27], ␣␣-cross-linked human hemoglobin (DCLHb) [6], rHb1.1 and rHb2.0 for injection. Of these compounds only the latter allowed for hemodilution without impairment of capillary perfusion.…”

Stem Cells for the Heart, Are We There Yet?

“…However, many of these mediators are still unknown and some are likely to be expressed transiently [21]. …”

“…However, caution is warranted because the induction of granulocytosis in patients with myocardial infarction during a course of G-CSF might contribute to the development of myocardial reperfusion injury or plaque destabilization at the remote, nonculprit coronary lesions [45, 47, 48]. Additionally, the use of this cytokine in humans might be ineffective when initiated at the time of acute ischemia and infarction due to competition for migration and receptor occupancy of the injured heart by other cells such as neutrophils [21]. Furthermore, the angiogenic effects of GM-CSF may also involve the vasa vasorum of atherosclerotic plaques which might worsen atherosclerotic disease.…”