Fluid resuscitation with hemoglobin vesicles in a rabbit model of acute hemorrhagic shock

Several hemoglobin (Hb)-based oxygen carriers are available for use in clinical situations, but their use risks inducing cardiovascular dysfunction as a result of Hb interacting with nitric oxide. Hb vesicles (HbV) are liposome-encapsulated purified human Hb with polyethylene glycol chains at the surface. This study evaluated the effects of HbV on hemodynamics, tissue and systemic oxygenation, and osmotic pressure after fluid resuscitation in an acute hemorrhagic shock model. Hemorrhagic shock was induced in 24 anesthetized mechanically ventilated male rabbits by withdrawing blood to a mean arterial blood pressure (MAP) of 30 to 35 mmHg over 15 min and maintaining this state for 30 min. The animals were resuscitated by replacing the blood with equal volumes of HbV in recombinant human albumin solution (HbV/rHSA), rHSA alone, or Ringer lactated solution (RL), or with three times the withdrawn volume of RL and observed for 2 h. Fluid resuscitation restored MAP, central venous pressure, and cardiac index values, but these fell again within 2 h in rabbits treated with RL. Fluid resuscitation using HbV/rHSA immediately increased MAP and cardiac index but not systemic vascular resistance, maintained a high level of oxygen consumption, and reduced the blood glucose level, which increased after hemorrhage. Fluid resuscitation using HbV/rHSA did not disturb microoxygenation in the brain, kidneys, liver, or muscle; allowed an immediate recovery of tissue oxygenation without decreasing cardiac output or increasing systemic vascular resistance, and increased the oxygen consumption. HbV solution offers the advantages of systemic oxygenation without impairing microcirculation in the treatment of hemorrhagic shock.