Resuscitation with polyethylene glycol-modified human hemoglobin improves microcirculatory blood flow and tissue oxygenation after hemorrhagic shock in awake hamsters

Objective: To determine whether resuscitation with polyethylene glycol-modified human hemoglobin (MalPEG-Hb), an oxygen-carrying blood replacement fluid with 4 g/dL Hb, viscosity of 2.5 cP, colloid osmotic pressure of 49 mm Hg, and p50 of 5.5 mm Hg, improves systemic and microvascular variables after hemorrhage compared with shed blood (SB) and 5% hydroxyethyl starch (HES). Setting. Laboratory. Subjects. Golden Syrian hamsters. Design. Prospective study. Interventions: Hamsters implemented with a skin fold chamber were hemorrhaged 50% of blood volume and resuscitated with 50% shed blood volume (SB, HES, or MalPEG-Hb). Measurements and Main Results., Shock and resuscitation were monitored for 1 hr each. Microvascular events were characterized in terms of vessel diameter, flow velocity, functional capillary density, and Po-2 in arterioles, venules, and extravascular tissue. Systemic variables include mean arterial pressure, heart rate, Po-2, Pco(2), pH, and base excess. MalPEG-Hb resuscitation increased functional capillary density to 64% vs. 44% for SB and 32% for HES relative to baseline before shock. Microvascular flow increased 16% for MalPEG-Hb relative to baseline and remained decreased by 44% for SB and 80% for HES. Hemoglobin concentration was 10.4 g/dL with SB, 7.5 (6.8 g/dL in red blood cells and 0.9 g/dL in plasma) with MalPEG-Hb, and 7.5 g/dL with HES, leading to tissue Po-2 of 19, 8, and 5 mm Hg respectively. Calculations of oxygen extraction show that 0.9 g/dL of MalPEG-Hb increased oxygen extraction per gram of red cell hemoglobin in the tissue analyzed compared with SB. These measurements correlate well with a systemic indicator of recovery, base excess, 5.4 +/- 4.7 (MalPEG-Hb), 1.7 +/- 3.8 (SB), and -0.3 +/- 5.7 (HES). Conclusion: The presence of 0.9 g/dL of high oxygen affinity MalPEG-Hb improves microvascular blood flow and oxygen transport during shock to a significantly greater extent than that attainable with blood or HES.