Filtration of diaspirin crosslinked hemoglobin into lung and soft tissue lymph.
Diaspirin crosslinked hemoglobin (DCHb) is a new blood substitute manufactured from human blood. To evaluate its microvascular filtration properties, we infused DCLHb into unanesthetized sheep (10%, 20 ml/kg) and measured the flow and composition of lung and soft tissue lymph. For comparison, we also infused human serum albumin (HSA; 10%, 20 ml/kg). DCLHb raised systemic and pulmonary arterial pressures from baseline values of 83 +/- 7 and 13 +/- 2 mm Hg, respectively, to peak values of 113 +/- 9 and 26 +/- 3 mm Hg (p < 0.05 versus baseline). These increases were significantly greater than those associated with HSA, which raised systemic and pulmonary arterial pressures from baseline values of 86 +/- 4 and 13 +/- 2 mm Hg, respectively, to peak values of 97 +/- 3 and 21 +/- 7 mm Hg (p <= 0.05 versus baseline and versus DCLHb). These differences reflect the known pressor properties of DCLHb. Accordingly, DCLHb raised lung and soft tissue lymph flows to peak values of 12.2 +/- 3.8 and 1.6 +/- 0.7 ml/30 min, respectively, while HSA raised lung and soft tissue lymph flows to peak values of 7.5 +/- 4.8 and 4.6 +/- 1.9 ml/30 min, respectively (p <= 0.05 versus DCLHb). The half-times of DCLHb equilibration from plasma into lung and soft tissue lymph of 1. 0 +/- 0.3 and 2.1 +/- 1.1 h, respectively, were significantly faster than HSA equilibration half-times of 3.1 +/- 0.2 and 3.8 +/- 0.9 h. Filtration differences between DCLHb and HSA appear to be due to the pressor properties DCLHb.
Department of Surgery, University of Wisconsin-Madison, and William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA.
R L
RL
Conhaim
S D
SD
Cooler
A M
AM
McGrath
D A
DA
DeAngeles
G A
GA
Myers
B A
BA
Harms
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005069:Evaluation Studies as Topic; D006207:Half-Life; D006400:Hematocrit; D006454:Hemoglobins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D006874:Hydrostatic Pressure; D008168:Lung / Q000378:metabolism*; D008196:Lymph / Q000378:metabolism*; D008833:Microcirculation / Q000378:metabolism; D009997:Osmotic Pressure; D011651:Pulmonary Artery; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012709:Serum Albumin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D012756:Sheep; D014018:Tissue Distribution
D001802:Blood Substitutes; D006454:Hemoglobins; D012709:Serum Albumin; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin