title: Effects of diaspirin-cross-linked hemoglobin (DCLHb) on the microcirculation of striated skin muscle in the hamster: a study on safety and toxicity.
abstract: Hemoglobin-based oxygen-carrying solutions are reported to exert vasoconstrictor effects and to enhance oxygen radical formation, particularly during ischemia-reperfusion. This study investigates whether diaspirin-cross-linked hemoglobin (DCLHb) affects the microvascular integrity of striated skin muscle. The microcirculation model in the hamster and intravital fluorescence microscopy were applied for investigation of the microvascular changes in striated skin muscle. Hypervolemic infusion (500 mg x kg(-1), I.V.) and isovolemic exchange transfusion (3.3 gm x kg(-1) I.V.; hematocrit 30%) with DCLHb (1) led to a short-lasting (0 to 2 minutes) arteriolar constriction (approximately 20% reduction in baseline diameter), (2) significantly influenced arteriolar vasomotion, (3) increased venular red blood cell velocity by 1.5-fold (p < 0.05 vs dextran, Mr 60,000), and (4) did not enhance microvascular leukocyte-endothelium interaction or endothelial permeability. Resuscitation from severe hemorrhagic shock with autologous blood (AuB) or DCLHb (33 ml x kg(-1), I.V.) immediately restored mean arterial pressure and heart rate, whereas 6% dextran (60 kd)(Dx-60) did not return these parameters to baseline. Venular red blood cell velocity was restored to 110% of baseline after DCLHb, to 90% of baseline after AuB, and to 45% of baseline after Dx-60. Leukocyte-endothelium interaction was significantly enhanced after resuscitation with AuB and Dx-60, whereas this phenomenon was absent after DCLHb. These data demonstrate that DCLHb increases venular red blood cell velocity under both nonischemic and postischemic conditions without inducing enhanced leukocyte-endothelium interaction in the microcirculation of striated skin muscle.
authors.affiliation: Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Nolte
authors.forename: A
authors.initials: A
authors.lastname: Botzlar
authors.forename: S
authors.initials: S
authors.lastname: Pickelmann
authors.forename: E
authors.initials: E
authors.lastname: Bouskela
authors.forename: K
authors.initials: K
authors.lastname: Messmer
mesh_terms: D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001802:Blood Substitutes / Q000494:pharmacology*; D001810:Blood Volume; D006224:Cricetinae; D015194:Diffusion Chambers, Culture; D004730:Endothelium, Vascular / Q000378:metabolism; D005078:Exchange Transfusion, Whole Blood; D006454:Hemoglobins / Q000494:pharmacology*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy; D012867:Skin / Q000098:blood supply* / Q000187:drug effects
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin