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

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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.