The fifth intercostal space was closed with a single surgical suture, and the skin and muscle incisions were closed with four loose sutures. The hilum was ligated with a 3–0 silk suture, and the lung was removed. A postero-lateral incision was made, followed by a thoracotomy at the fifth intercostal space. Blood samples were obtained to determine the values on mechanical ventilation. The rats were orotracheally intubated with a 14 G catheter and connected to a rodent ventilator (model SN-480-7 Shinano, Tokyo, Japan) adjusted to maintain a respiratory rate of 60 breath/min, tidal volume of 10 mL/kg, positive end-expiratory pressure of 2 cmH 2O and inspired O 2 concentration of 0.21. Surgical procedures for left pneumonectomy In the present study, the immediate effects of systemic administration of HbVs or low-P 50 HbVs were evaluated after massive blood exsanguination in a rat pneumonectomy model. These effects may facilitate rapid stabilisation of haemodynamics and oxygenation in cases showing massive surgical haemorrhage during lung resection, which can cause remarkable reductions in pulmonary function. We expect low-P 50 HbVs to help improve oxygen intake at the lung and carry more oxygen into organ tissues in animals that undergo lung resection. In previous investigations on tumour oxygenation, low-P 50 HbVs increased tissue partial oxygen pressure and facilitated the effects of irradiation on tumours. 7 The oxygen affinity of normal HbVs is set at a P 50 level of 28 Torr, and that of HbVs with high oxygen affinity is set at a P 50 level of 9 Torr (low-P 50 HbVs). 6 They are expected to show various clinical applications, including management of surgical haemorrhage, in the near future, although all trials for the clinical application of other artificial oxygen carriers developed as substitutes for RBC transfusion have ended in failure due to side effects or a lack of effectiveness.Ī notable characteristic of HbV is that its oxygen affinity can be modified by changing the allosteric effectors encapsulated with the purified haemoglobin in the vesicles. HbVs can be preserved for years and used irrespective of the blood type and are free from the risk of infection. Haemoglobin is extracted from outdated human red blood cells (RBCs) for transfusion, purified and virus-inactivated and then encapsulated in liposomes 5 with a polyethylene modified surface (diameter=250 nm P 50=28 Torr). Haemoglobin vesicles (HbVs), which are liposomes-containing concentrated haemoglobin, were developed as artificial oxygen carriers that serve as an alternative to transfusion. McKenna et al reported that blood transfusion was required in 45 of 1100 patients (4.1%) who underwent thoracic lobectomy. However, the risks of massive surgical haemorrhage remain unchanged because pulmonary vessels are fragile, and malignant tumours may invade these vessels. 3 Advances in surgical technology and anaesthesia techniques have enabled lung resection to be performed safely. 1 2 Surgery offers the best chances for cure in patients with early stage non-small cell lung cancer. Lung cancer is a highly lethal disease in many countries.
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