Plasma volume expanders are often required in the management of critical care patients, who are frequently hypoproteinemic, or who have sepsis- induced increases in microvascular permeability. Volume expanders frequently employed include dextran-70, pentafraction, and hetastarch. However, these compounds are composed of a broad range of molecular fractions, and we hypothesize that the smaller fractions, less that 150 kilodaltons (kD), can filter into lung and soft tissue lymph. If this is true it means that the oncotic effectiveness of these solutions is compromised, because in addition to raising the oncotic pressure of the plasma, they would also raise the oncotic pressure of the lymph. This would facilitate vascular filtration and enhance development of lung systemic edema. We propose to test our hypothesis in unanesthetized sheep by measuring oncotic pressures contributed by each of the three volume expanders named above, and by using high performance liquid chromatography (HPLC) to measure their molecular weight distributions in plasma and lymph. Few previous studies have addressed the possibility of volume expander filtration, and to our knowledge, no previous studies have compared starch oncotic pressures nor starch molecular weight profiles between plasma and lymph. Results of such a study are important because they would identify a molecular weight that would result in minimum macromolecular filtration, which could lead to development of an improved volume expander that would exert maximum oncotic effectiveness. Dextran-70, pentafraction and hetastarch have average molecular weights, respectively, of 70, 200, and 450 kD, but the distributions around these averages are quite broad. For example, 80% of dextran-70 ranges from 20 to 200 kD, 80% of pentafraction ranges from 40 to 1,250 kD, and 80% of hetastarch ranges from 25 to 3,000 kD. Our hypothesis implies that dextran-70 should readily enter lymph and enhance filtration because the majority of its molecules are smaller that 150 kD; a recent report confirms this. The smaller pentafraction and hetastarch fractions should also filter, and so should albumin, which has a molecular weight of 66 kD. (The largest fractions in hetastarch are also undesirable and are thought to be associated with coagulopathies.) Sheep, prepared for long-term collection of lung and soft tissue lymph, will be infused with dextran-70, pentafraction, or hetastarch. Autogenous plasma will also be infused for comparison. Plasma and lymph samples will be collected, and starch oncotic pressures and molecular weight distributions will be measured. The solutions will be infused in normal and hypoproteinemic conditions, and in conditions in which vascular permeability is increased.
