Characterization of the Hemodynamic Response to Intravenous Diaspirin Crosslinked Hemoglobin Solution in Rats

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Abstract
Diaspirin crosslinked hemoglobin solution (DCLHB) has potential for clinical use as an oxygen-carrying solution because of its excellent oxygen transport properties and biochemical stability. The present study characterizes the effects of intravenous infusions of 0.625-40 mL/kg (62.5-4000 mg/kg) DCLHb on mean blood pressure (MAP) and heart rate (HR) in conscious rats. DCLHb at all doses tested except 62.5 mg/kg was associated with an immediate increase in MAP (25-30% above baseline) that peaked between 20-30 minutes after infusion and returned to baseline within 120-300 minutes in a dose-dependent manner. Maximum MAP achieved was in the range of 129 +/- 7 to 140 +/- 7 mm Hg and there was no statistically significant difference in the response between doses. HR responded in a reciprocal manner to changes in MAP. Volume- and oncotic-matched infusions of LR and albumin did not alter MAP or HR. Slow infusion (0.34 mL/min) of DCLHb appeared to blunt the magnitude of the pressor response when compared to bolus injection (< 10 sec). DCLHb administration is associated with a pressor response that is not due to volume load, oncotic pressure, or rate of infusion, suggesting that it is intrinsic to the modified hemoglobin molecule and pharmacologic in nature.