Clearance of differentially labelled infused hemoglobin and polymerized hemoglobin from dog plasma and accumulation in urine and selected tissues.

Abstract

Pyridoxalated hemoglobin polymerized with glutaraldehyde has been proposed as a hemoglobin based blood substitute. The preparations contain significant amounts of unpolymerized hemoglobin. We have prepared polymerized pyridoxalated hemoglobin labelled with 14C by reductive methylation free of unpolymerized hemoglobin and pyridoxalated hemoglobin labelled with 3H by reductive methylation to compare the handling of the two forms after infusion into dogs. Four dogs were examined sequentially. After three hours, 52.4 +/- 8.9% of the 3H label had disappeared from plasma whereas 21.7 +/- 5.8 of the 14C label had disappeared. The decrease of both labels occurred in a very close to linear fashion over the time period examined. From radioactivity in collected urine, it was calculated that 30.7 +/- 6.3% of the 3H and 9.0 +/- 2.7 of the 14C that had been cleared from plasma appeared in urine. The ratio of the specific radioactivity in tissue to the specific radioactivity of plasma indicated that extravascular accumulation of 3H label from unpolymerized hemoglobin occurred in kidney, heart and liver, with the kidney cortex exhibiting a very high concentration of the label. The specific radioactivity of both 3H and 14C label in liver suggested the substantial involvement of the reticuloendothelial system in the removal of both unpolymerized and polymerized hemoglobin from the circulation.