Small-Volume Resuscitation From Hemorrhagic Shock Using High-Molecular-Weight Tense-State Polymerized Hemoglobins

Background: The objective of this study was to determine the role of plasma oxygen carrying capacity during resuscitation from hemorrhagic shock (HS). Methods: Hemodynamic responses to small-volume resuscitation from HS with hypertonic saline followed by infusion of ultrahigh-molecular-weight tense-state polymerized hemoglobins (PolyHbs) were studied in the hamster window chamber model. HS was induced by withdrawing 50% of the blood volume (BV), and hypovolemic state was maintained for 1 hour. Resuscitation was implemented by infusion of hypertonic saline (3.5% of BV) followed by 10% of BV infusion of polymerized human Hb (PolyHb(hum), P-50 = 49 mm Hg), polymerized bovine Hb (PolyHb(bov), P-50 = 40 mm Hg), or human serum albumin (HSA), all at 10 g/dL. Resuscitation was monitored over 90 minutes. Results: PolyHb(hum) elicited higher arterial pressure, produced vasoconstriction, and decreased perfusion. In contrast, PolyHb(bov) and HSA exhibited lower blood pressure and partially restored perfusion and functional capillary density compared with PolyHb(hum). Blood gas parameters showed a pronounced recovery after resuscitation with PolyHb(bov) compared with both PolyHb(hum) and HSA. Tissue PO2 was significantly improved in the PolyHb(bov) group, showing that the moderate increase in P-50 of PolyHb(bov) compared with hamster blood (P-50 = 32 mm Hg) was beneficial during resuscitation. However, an excessive increase in oxygen release between the central and peripheral circulation, as induced by PolyHb(hum) produced vasoconstriction and hypoperfusion, limiting the benefits of additional oxygen carrying capacity. Conclusions: Appropriately engineered PolyHb will enhance/reinstate oxygenation, without hypertension or vasoconstriction, to be used in situations where blood transfusion is not logistically feasible.