Experimental use of Liposome-encapsulated hemoglobin to improve microcirculation and oxygenation

背景。我们验证了一个假设，即具有高氧亲和力（P_<50>=10 mmHg）的超小（200 nm）脂质体包封血红蛋白（LEH）可能限制循环功能不全（如脑缺血（CI），心肌缺血（MI））和增强肿瘤放疗的缺血损伤。缺血。阻断大鼠右侧大脑中动脉前后5分钟静脉滴注1%体重的LEH。24小时后用MRI系统获得的皮质纹状体、海马和梨状叶T2加权相对信号强度与未治疗的CI大鼠的水肿严重程度进行比较。LEH对大鼠除梨状叶外各脑区水肿均有明显减轻作用。LEH对大鼠脑缺血前后脑水肿均有明显的减轻作用。心肌缺血。在左前降支闭塞后10分钟和40分钟，再灌注后20分钟，分别用LEH或1%体重的生理盐水预处理大鼠，分析压力-容量循环。虽然舒张末期和收缩期末期左心室容积没有差异，但leh处理大鼠的卒中容积、舒张末期压和射血分数均有显著保留。NRC（0.5%, 1%， 2%体重）在小鼠植入性鳞状细胞癌放射治疗前30,60,90和120分钟静脉输注。放疗前30分钟输注1% NRC最有效，肿瘤生长时间从未治疗时的20天延长至26天，延长5倍。高o_2亲和LEH能有效改善脑缺血和心肌缺血，增强放射治疗对肿瘤生长的抑制作用。最佳剂量、时间和o_2亲和力有待进一步确定。

Background. We tested a hypothesis that an ultra-small (200 nm) liposome-encapsulated-hemoglobin (LEH) with a high oxygen affinity (P_<50>=10 mmHg) may limit ischemia damages in circulatory insufficiency such as cerebral ischemia (CI), myocardial ischemia (MI) and potentiate tumor radiotherapy.Cerabral Ischemia. LEH was intravenously infused 1% of body weight 5 minutes before and after occlusion of the right middle cerebral artery in rats. Severity of edema was compared with CI rats without treatment 24-hour later on T2 weighed relative signal strength obtained with MRI system at cortex1 striatum, hippocampus and pyriform lobe. LEH was effective in reducing brain edema in all areas except in pyriform lobe in LEH-treated rats. LEH was effective in reducing brain edema before as well as after CI in the rat.Myocardial Ischemia. Pressure-volume loops were analyzed 10 and 40 minutes after occlusion of the left anterior descending artery and 20 minutes after reperfusion in rats pretreated with LEH or saline of 1% body-weight. Although end-diastolic or end-systolic left ventricular volumes were not different, stroke volume, end-diastolic pressure and ejection fraction were significantly preserved in LEH-treated rats.Neoplasm. NRC (0.5%, 1%, 2% of body weight) was intravenously infused 30, 60, 90 and 120 minutes before radiation therapy on implanted squamous cell carcinoma in mice. NRC was most effective when 1% NRC infusion 30 minutes prior to radiation, which prolonged 5-times tumor -growth time from 20 days (no treatment) to 26 days.Conclusion. High-O_2-affinity LEH was effective to ameliorate cerebral and myocardial ischemia and potentiate radiation therapy against tumor growth. Optimal dose, timing and O_2-affinity need to be further defined.