title: Effects of ultra-purified polymerized bovine hemoglobin on the microcirculation of striated skin muscle in the hamster.
abstract: 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.
authors.affiliation: Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilian's University of Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Botzlar
authors.forename: D
authors.initials: D
authors.lastname: Nolte
authors.forename: K
authors.initials: K
authors.lastname: Messmer
mesh_terms: D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D002417:Cattle; D006224:Cricetinae; D006454:Hemoglobins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000503:physiopathology; D012867:Skin / Q000098:blood supply
chemical_list: D006454:Hemoglobins