ACUTE CHANGES IN SYSTEMIC BLOOD-PRESSURE AND URINE OUTPUT OF CONSCIOUS RATS FOLLOWING EXCHANGE-TRANSFUSION WITH DIASPIRIN-CROSS-LINKED HEMOGLOBIN SOLUTION

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 (alphaalphaHb). Stroma-free Hb was crosslinked between the alpha chains by using a C-14-labeled diaspirin, bis(3,5-dibromosalicyl)fumarate. Forty conscious, chronically cannulated rats underwent ET with C-14-labeled alphaalphaHB 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 1 20 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 alphaalphaHb 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 alphaalphaHb was 5 hours (administered dose, 2.4 g Hb/kg body weight). Thus, infusion of alphaalphaHb caused a transient systemic hypertension, and intramolecular crosslinking alone was not enough to exclude completely the filtration of alphaalphaHb by the kidneys.