Heneka M T, Löschmann P A, Osswald H
Department of Pharmacology, University of Tübingen, Germany.
J Clin Invest. 1997 Jan 1;99(1):47-54. doi: 10.1172/JCI119132.
Sepsis and its complications, hypotension, shock, and multiorgan failure continue to represent a significant cause of mortality among hospitalized patients, affecting approximately 200,000 patients per year in the US and 100,000 in Europe (Dal Nogare, A.R. 1991. Am. J. Med. Sci. 302:50-65.). Incidence rates appear to be increasing, probably due to an increase in the population with risk factors such as diabetes or invasive procedures. Activation of cytokines by endotoxins and subsequent formation of nitric oxide is of central pathogeneic importance in sepsis. In this study we show that polymerized bovine hemoglobin (Biopure 2) restores both cardiovascular and renal functions in an endotoxin-induced shock model in rats. These effects are compared to those of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine, and hydroxyethyl starch, the latter currently in clinical use for intravenous volume replacement. Our results clearly indicate that polymerized hemoglobin but not nitric oxide synthase inhibition or volume replacement normalize cardiovascular and kidney function in acute septic shock. This new therapeutic approach is readily applicable to controlled clinical trials because polymerized hemoglobin has been tested in humans and is therefore available for such studies.
脓毒症及其并发症，如低血压、休克和多器官功能衰竭，仍然是住院患者死亡的一个重要原因，在美国每年影响约200,000名患者，在欧洲每年影响100,000名患者（达尔·诺加雷，A.R. 1991年。《美国医学科学杂志》302:50 - 65）。发病率似乎在上升，这可能是由于糖尿病或侵入性操作等危险因素人群的增加。内毒素激活细胞因子以及随后一氧化氮的形成在脓毒症的发病机制中具有核心重要性。在本研究中，我们表明聚合牛血红蛋白（Biopure 2）在大鼠内毒素诱导的休克模型中可恢复心血管和肾功能。将这些作用与一氧化氮合酶抑制剂N(G)-硝基-L-精氨酸以及羟乙基淀粉的作用进行比较，羟乙基淀粉目前在临床上用于静脉补液。我们的结果清楚地表明，在急性脓毒性休克中，聚合血红蛋白而非一氧化氮合酶抑制或补液可使心血管和肾功能恢复正常。这种新的治疗方法很容易应用于对照临床试验，因为聚合血红蛋白已在人体中进行过测试，因此可用于此类研究。
