Physiologic responses of cross-linked hemoglobin in endotoxin-treated rats

作     者：Goff, JM Jackson, MR Taher, M Cutting, MA Alving, BM Krishnamurti, C 

作者机构：Walter Reed Army Inst Res Dept Hematol & Vasc Biol Washington DC 20307 USA Walter Reed Army Med Ctr Dept Surg Washington DC 20307 USA 

出 版 物：《ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY》 (Artif. Cells Blood Substitutes Immobilization Biotechnol.)

年 卷 期：1999年第27卷第1期

页      面：11-21页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 1007[医学-药学(可授医学、理学学位)] 0805[工学-材料科学与工程（可授工学、理学学位）] 0836[工学-生物工程] 10[医学] 

主　　题：麻醉 血压/药物作用 药物协同作用 内皮缩血管肽1/血液 内毒素类/毒性 血红蛋白类/代谢 血红蛋白类/药理学 低血压/化学诱导 低血压/死亡率 脂多糖类/药理学 一氧化氮/血液 亚硝酸盐类/尿 大鼠 Sprague-Dawley 动物 人类 男(雄)性 兔 大鼠 

摘      要：Purified human cross-linked hemoglobin (alpha alpha Hb) as well as recombinant human hemoglobin is undergoing clinical trials in the setting of acute brood loss and perioperative hemodilution. We have previously demonstrated that in rabbits with circulating plasma Hb, such as alpha alpha Hb, infusion of endotoxin (LPS) impairs myocardial contractility which results in hypotension, tissue hypoperfusion and increased mortality. The untoward cardiovascular effects occurring after the combined infusion of LPS and alpha alpha Hb in this model are similar to those reported for other agents that inhibit nitric oxide (NO) availability. To determine if the deleterious effects of alpha alpha Hb and LPS were species specific, we performed similar studies in rats. Anesthetized Sprague-Dawley rats received LPS (4 mg/kg or 40 mg/kg) alone or in combination with alpha alpha Hb (0.7 g/kg). Mean arterial blood pressures (MAP) increased in the group that received alpha alpha Hb alone (105+/-8 to 120+/-7 mm Hg, p=0.2) and a decrease was noted in the groups that received low dose LPS (4 mg/kg, p=0.5) and high dose LPS (40 mg/kg, p=0.016). MAP in rats treated with the LPS at either dose combined with alpha alpha Hb remained unchanged. Levels of urine nitrite, which was measured as a surrogate marker for plasma NO, were significantly decreased at 2 hr in groups that received the combination of alpha alpha Hb and LPS at 4 mg/kg (p=0.022) and 40 mg/kg (p=0.003). No significant decrease was observed in animals treated only with alpha alpha Hb (p=0.21) or LPS (4 mg/kg;p=0.78 and 40 mg/kg;p=0.65). Survival was evaluated during 72 hr in animals that were infused with high dose LPS (40 mg/kg) alone or in combination with alpha alpha Hb and then allowed to recover. The survival of rats treated with LPS alone or the combination was 29% at the end of 24 hr and was 100% for rats receiving only alpha alpha Hb. The data suggest that the toxicity of alpha alpha Hb appears to be a species specific phen