Immediate effects of systemic administration of normal and high O 2 -affinity haemoglobin vesicles as a transfusion alternative in a rat pneumonectomy model

Abstract

Background Haemoglobin vesicles (HbVs) are red blood cell (RBC) substitutes with a phospholipid bilayer membrane and a polyethylene modified surface (diameter=250 nm; P 50 =28 Torr). They can be preserved for years and can be used in patients of all blood types without the risk of infection. Their oxygen affinity can be modified by changing the allosteric effectors. Methods Left pneumonectomy was performed under mechanical ventilation on rats, followed by rapid exsanguination of ∼30% of the total circulating blood volume. Rat RBCs shed in 5% human serum albumin (HSA) solution (rat RBC), HbV with high oxygen affinity in 5% albumin solution (low-P 50 HbV, P 50 =9 Torr), normal HbV suspended in 5% albumin (HbV, P 50 =28 Torr) or 5% HSA was infused for resuscitation. Haemodynamics and oxygenation were evaluated. Results Systemic arterial blood pressure significantly decreased after exsanguination and increased after each infusion. In the HbV, low-P 50 HbV and rat RBC groups, all rats were liberated from mechanical ventilation and blood pressure was stabilised, whereas 50% of the rats in the HSA group died within 1 hour after weaning from mechanical ventilation. The PaO 2 in arterial blood for 1 hour after liberation from mechanical ventilation in the rat RBC, HbV and low-P 50 HbV groups was 59.4±12.5, 58.3±10.1 and 70.5±14.5 mm Hg, respectively. The PaO 2 in the low-P 50 HbV group was significantly higher than those in the rat RBC and HbV groups (p=0.05 for both). Serum lactate elevations due to hypoxic damage were minimised by HbV, low-P 50 HbV as well as rat RBCs. Conclusions The oxygen-carrying ability of HbV was comparable to that of rat RBCs, even under impaired lung function after pneumonectomy. HbVs with high oxygen affinity may have more beneficial effects on oxygenation in pulmonary resection.