Resuscitation with recombinant hemoglobin rHb2.0 in a rodent model of hemorrhagic shock.
BACKGROUND
Hemoglobin solutions combine volume effect, oxygen-carrying capacity, and vasoactive properties, the latter facilitating restoration of global hemodynamics but endangering microvascular resuscitation. Hemoglobin-evoked vasoconstriction probably is due to nitric oxide scavenging, which can be reduced by genetic modifications of the heme pocket. This study compares resuscitation with a nonhemoglobin colloid and two recombinant hemoglobin solutions with wild-type and reduced nitric oxide-scavenging capacity.


METHODS
Twenty-seven awake Syrian golden hamsters fitted with dorsal skinfold chambers underwent a 30 min-hemorrhagic shock (mean arterial pressure [MAP] 30-35 mmHg) and resuscitation with shed blood volume of either 6% dextran 60 (Biophausia, Uppsala, Sweden), recombinant hemoglobin 1.1 (rHb1.1; wild-type nitric oxide-scavenging capacity; 10 g/dl), or recombinant hemoglobin 2.0 (rHb2.0; reduced nitric oxide-scavenging capacity; 10 g/dl; both Baxter Healthcare, Boulder, CO). Macrohemodynamic and laboratory parameters were assessed; microvascular parameters in the skinfold chamber were analyzed by intravital microscopy.


RESULTS
Hemorrhagic shock reduced functional capillary density (FCD) by 70% and caused significant metabolic acidosis. Colloid resuscitation led to incomplete recovery of MAP and FCD. Infusion of rHb1.1 completely restored MAP but not FCD, with the smallest arteriolar diameters found in this group. FCD was restored best by resuscitation with rHb2.0, although MAP was lower than in rHb1.1-treated animals. Metabolic acidosis was resolved by both hemoglobin solutions, but not by dextran.


CONCLUSIONS
After resuscitation with rHb1.1, arteriolar vasoconstriction quickly restored MAP, but this was achieved at the expense of FCD. In contrast, after resuscitation with rHb2.0, the recovery of MAP could be translated into a significantly improved FCD.
Hermann
Joerg
J
Institute for Surgical Research, Ludwig-Maximilians-University, Munich, Germany.
Corso
Carlos
C
Messmer
Konrad F
KF
D000138:Acidosis / Q000188:drug therapy; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000627:therapeutic use*; D006224:Cricetinae; D003911:Dextrans / Q000008:administration & dosage; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000627:therapeutic use*; D006455:Hemoglobins, Abnormal / Q000627:therapeutic use*; D008833:Microcirculation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply; D009569:Nitric Oxide / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D014661:Vasoconstriction / Q000187:drug effects
D000925:Anticoagulants; D001802:Blood Substitutes; D003911:Dextrans; C474711:HBOC rHB2.0, human; D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D011994:Recombinant Proteins; C105876:hemoglobin rHb1.1; D009569:Nitric Oxide