Hughes G S, Yancey E P, Albrecht R, Locker P K, Francom S F, Orringer E P, Antal E J, Jacobs E E
Upjohn Company, Kalamazoo, MI 49001, USA.
Clin Pharmacol Ther. 1995 Oct;58(4):434-43. doi: 10.1016/0009-9236(95)90057-8.
The objective of this study was to evaluate the exercise capacity of subjects given an autologous transfusion or a polymerized bovine hemoglobin solution to define the pharmacodynamics and pharmacokinetics of a new hemoglobin-based oxygen carrier (HBOC-201).
Six normal healthy male subjects (ages 25 to 45 years) participated in this randomized, single-blind, two-way crossover study, which took place at Upjohn Research Clinics in Kalamazoo, Mich. A radial artery catheter was inserted in each subject before serial cardiac output and pulmonary function tests and phlebotomy of 15% blood volume (750 ml plus another 250 ml for study laboratories yields 1000 ml, or about 150 gm human hemoglobin). This was followed by isovolemic hemodilution with Ringer's lactate plus an autologous blood transfusion (or HBOC-201) and 1 week later 45 gm bovine hemoglobin of HBOC-201 (or autologous transfusion). Bicycle exercise stress tests to anaerobic threshold (approximately 65% of predicted maximum aerobic capacity) were done before phlebotomy and at approximately 45 minutes after the autologous transfusion or HBOC-201 infusion.
Subjects had similar exercise and diffusion capacity but lower lactate levels (for up to 24 hours) during HBOC-201 (which paralleled plasma HBOC-201 levels) than during autologous transfusion periods. Oxygen use (uptake) and carbon dioxide production at rest were greater during the HBOC-201 infusion than during the autologous transfusion period. The half-life of HBOC-201 was about 23 hours.
Exercise capacity and diffusion capacity were similar after HBOC-201 and autologous transfusion. HBOC-201 resulted in greater oxygen (or uptake) and carbon dioxide production and lower lactate levels compared with autologous transfusion. Under the conditions of the study, the physiologic effects of 1 gm bovine hemoglobin of HBOC-201 were similar to 3 gm human hemoglobin from autologous transfusion.
本研究的目的是评估接受自体输血或聚合牛血红蛋白溶液的受试者的运动能力，以确定一种新型基于血红蛋白的氧载体（HBOC-201）的药效学和药代动力学。
六名正常健康男性受试者（年龄25至45岁）参与了这项随机、单盲、双向交叉研究，该研究在密歇根州卡拉马祖的Upjohn研究诊所进行。在进行系列心输出量和肺功能测试以及抽取15%血容量（750毫升加上另外250毫升用于研究实验室，共1000毫升，约150克人血红蛋白）之前，为每位受试者插入桡动脉导管。随后进行用乳酸林格氏液的等容血液稀释以及自体输血（或HBOC-201），1周后输注45克HBOC-201的牛血红蛋白（或自体输血）。在放血前以及自体输血或HBOC-201输注后约45分钟进行自行车运动应激测试至无氧阈（约为预测最大有氧能力的65%）。
与自体输血期间相比，受试者在输注HBOC-201期间（与血浆HBOC-201水平平行）具有相似的运动和扩散能力，但乳酸水平较低（长达24小时）。在输注HBOC-201期间静息时的氧摄取和二氧化碳产生量高于自体输血期间。HBOC-201的半衰期约为23小时。
输注HBOC-201和自体输血后的运动能力和扩散能力相似。与自体输血相比，HBOC-201导致更高的氧摄取和二氧化碳产生以及更低的乳酸水平。在本研究条件下，1克HBOC-201的牛血红蛋白的生理效应与3克自体输血的人血红蛋白相似。
