This report describes acute changes in systemic blood pressure and urine output observed after a 50-percent isovolemic exchange transfusion (ET) with
diaspirin-crosslinked
hemoglobin (
alpha alpha Hb). Stroma-free Hb was crosslinked between the alpha chains by using a 14C-labeled
diaspirin,
bis(3,5-dibromosalicyl)fumarate. Forty conscious, chronically cannulated rats underwent ET with 14C-labeled
alpha alpha Hb solution (8.0 g/dL [80 g/L]). This resulted in systemic
hypertension for 3 to 4 hours after ET (mean arterial pressure rose from 120 to 145 torr at 1 to 2 hours after ET) and mild
bradycardia for 2 to 3 hours (heart rate decreased from 420 to 335 beats/min [bpm] before stabilizing at 360 +/- 10 bpm). This was accompanied by significant diuresis immediately after ET (5- 6-fold increase in urine output, which normalized after 12 hours), and mild
hemoglobinuria. The total amount of Hb recovered in the urine was < 5 percent of the injected dose. Reversed-phase high-performance liquid chromatography and
sodium dodecyl sulfate-
polyacrylamide gel electrophoresis confirmed the presence of crosslinked
alpha alpha Hb molecules in the urine. Renal excretion of radioactivity was significantly greater, with 20 percent of total radioactivity being eliminated within 24 hours. The plasma half-life for
alpha alpha Hb was 5 hours (administered dose, 2.4 g Hb/kg
body weight). Thus, infusion of
alpha alpha Hb caused a transient systemic
hypertension, and intramolecular crosslinking alone was not enough to exclude completely the filtration of
alpha alpha Hb by the kidneys.