DIASPIRIN CROSS-LINKED HEMOGLOBIN - TISSUE DISTRIBUTION AND LONG-TERMEXCRETION AFTER EXCHANGE-TRANSFUSION

This report describes the tissue distribution and long-term (14-day) e xcretion of hemoglobin cross-linked between the alpha-chains (alpha al pha Hb) with carbon 14-labeled bis(3,5-dibromosalicyl)fumarate. Fully conscious, chronically cannulated rats (n = 40) were treated with a 50 % isovolemic exchange transfusion (ET) with solutions of C-14-labeled alpha alpha Hb (8.0 gm/dl) and were then monitored for as long as 14 d ays. Thirteen tissue types were analyzed for radioactivity by liquid s cintillation counting. The highest concentration of label was found in the kidney and in tissues of the reticuloendothelial system (i.e., sp leen, bone marrow, and liver). The C-14-labeled alpha alpha Hb did not appear to cross the blood-brain barrier, because radioactivity in the brain was barely detectable. The dose of C-14-labeled alpha alpha Hb (2.4 gm Hb/kg) produced an initial plasma Hb level of 4.6 gm/dl, with a half-life in the plasma of 5.0 hours. The peak concentration in kidn ey, spleen, and liver occurred at 24 hours after ET, when at least 92% of the C-14-labeled alpha alpha Hb in plasma had been cleared. At 48 hours, red casts were seen in a tiny number of renal tubules in some r ats. By 14 days, up to 64% of the injected radioactivity had been reco vered in urine and about 10% was recovered in feces. Most excretion oc curred 24 to 48 hours after ET. This study demonstrated that 2 weeks w ere required for the metabolic degradation and elimination of a large dose of alpha alpha Hb in rats.