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.

Molecular distribution of hetastarch in plasma and lung lymph of unanesthetized sheep.

We used high performance size exclusion chromatography (HPSEC) to measure concentrations and molecular masses of hetastarch (Het) in plasma and lung lymph of unanesthetized sheep. Our goal was to assess the osmotic effectiveness of Het in the pulmonary circulation as judged by its exclusion from lung lymph. Sheep (n = 5) received 35 ml/kg of Het (6%) over 90 min. At the end of the infusion, Het concentrations in plasma reached a peak value of 2.9 +/- 0.1% (mean +/- SD). Lymph concentrations reached a peak value of 1.3 +/- 0.3% at 4.5 h. Het molecular masses in plasma averaged 650 +/- 36 kD at 90 min, but ranged from 31 to 2,942 +/- 187 kD. Masses in lung lymph averaged 373 +/- 71 kD, and ranged from 19 +/- 2 to 1,693 +/- 514 kD (p < or = 0.05 vs. plasma). Het contributed 6.7 +/- 1.5 mm Hg to the plasma macromolecular osmotic pressure, and 3.7 +/- 1.8 mm Hg to the lymph osmotic pressure. Despite the fact that Het has the largest molecular mass of any of the current macromolecular plasma volume expanders, we found that it filtered readily into lymph, raising the lymph osmotic pressure. These findings suggest that the rationale for the osmotic performance of such solutions may need to be reconsidered.

Resuscitation from hemorrhagic shock with diaspirin cross-linked hemoglobin, blood, or hetastarch.

BACKGROUND: An oxygen-transporting hemoglobin solution should be more effective than a nonhemoglobin solution for resuscitation from hemorrhagic shock. A way to evaluate this effectiveness is to determine whether a hemoglobin solution can reverse the base deficit accumulated during hemorrhage at a faster rate than a nonhemoglobin solution. Using this criterion, we compared the resuscitative powers of autologous blood, hetastarch (Het), and diaspirin cross-linked hemoglobin (DCLHb). METHODS: Fifteen sedated, spontaneously breathing sheep (37.5 +/- 10.2 kg) were bled until base deficits fell to -5 to -10 mEq/L, and plasma lactate concentrations rose to 6 to 9 mg/L. The animals were resuscitated with autologous blood (n = 5), Het (n = 5), or DCLHb (n = 5) (3.5-4.0 mL/kg every 15 minutes) until base deficits returned to prehemorrhage baseline. RESULTS: Exsanguination to target base deficits required removal of an average of 41.4 +/- 5.5 mL blood/kg (estimated total blood volume, 80 mL/kg). Resuscitation required 18 +/- 3, 38 +/- 2 (different from blood), and 35 +/- 1 (different from blood) mL/kg of autologous blood, Het and DCLHb, respectively, over periods of 78 +/- 8, 163 +/- 10 (different from blood), and 129 +/- 9 minutes (different from blood and different from Het (p < or = 0.05)). Based on regression analysis, autologous blood, Het, and DCLHb corrected the base deficit at rates of, respectively, 0.074 (different from Het (p < or = 0.05)), 0.016, and 0.056 (different from Het (P < or = 0.05)) mEq/L/min. CONCLUSIONS: Based on the rate of base deficit correction and the volume of solution required, autologous blood was the most effective resuscitation solution. However, DCLHb was more effective than Het. DCLHb may be an attractive alternative to blood for resuscitation from hemorrhagic shock.

Lung lymph oncotic pressure may not modulate pulmonary vascular filtration in sheep.

We tested the hypothesis that plasma oncotic pressure alone, not the plasma-to-lymph oncotic pressure difference, modulates pulmonary transvascular fluid filtration. To do this we measured lung lymph flow after raising left atrial pressure (by inflating a balloon) in sheep that were receiving a continuous (32 h) infusion of dextran 40. For comparison, we also raised left atrial pressure elevation, plasma oncotic pressures in dextran and control sheep, respectively, were 39.5 +/- 4.5 and 17.7 +/- 2.2 mm Hg; plasma-to-lymph oncotic pressure gradients, respectively, were 4.4 +/- 0.6 and 4.4 +/- 0.6 mm Hg. Left atrial pressure elevation during dextran infusion increased lung lymph flow by a factor of 2.4 +/- 0.4, compared with a factor of 4.2 +/- 2.3 in control sheep. Thus, left atrial pressure elevation increased lymph flow less in dextran-treated animals than in control animals, even though the plasma-to-lymph oncotic pressure gradients were equal. This suggests that plasma oncotic pressure alone may be a more important determinant of pulmonary transvascular fluid filtration than the plasma-to-lymph oncotic pressure difference.