用聚乙二醇修饰的人血红蛋白进行复苏可改善清醒仓鼠失血性休克后的微循环血流和组织氧合。

Resuscitation with polyethylene glycol-modified human hemoglobin improves microcirculatory blood flow and tissue oxygenation after hemorrhagic shock in awake hamsters.

作者信息

Wettstein Reto, Tsai Amy G, Erni Dominique, Winslow Robert M, Intaglietta Marcos

机构信息

Department of Bioengineering, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.

出版信息

Crit Care Med. 2003 Jun;31(6):1824-30. doi: 10.1097/01.CCM.0000069340.16319.F2.

DOI:10.1097/01.CCM.0000069340.16319.F2

PMID:12794426

Abstract

OBJECTIVE

To determine whether resuscitation with polyethylene glycol-modified human hemoglobin (MalPEG-Hb), an oxygen-carrying blood replacement fluid with 4 g/dL Hb, viscosity of 2.5 cP, colloid osmotic pressure of 49 mm Hg, and p50 of 5.5 mm Hg, improves systemic and microvascular variables after hemorrhage compared with shed blood (SB) and 5% hydroxyethyl starch (HES).

SETTING

Laboratory.

SUBJECTS

Golden Syrian hamsters.

DESIGN

Prospective study.

INTERVENTIONS

Hamsters implemented with a skin fold chamber were hemorrhaged 50% of blood volume and resuscitated with 50% shed blood volume (SB, HES, or MalPEG-Hb).

MEASUREMENTS AND MAIN RESULTS

Shock and resuscitation were monitored for 1 hr each. Microvascular events were characterized in terms of vessel diameter, flow velocity, functional capillary density, and Po(2) in arterioles, venules, and extravascular tissue. Systemic variables include mean arterial pressure, heart rate, Po(2), Pco(2), pH, and base excess. MalPEG-Hb resuscitation increased functional capillary density to 64% vs. 44% for SB and 32% for HES relative to baseline before shock. Microvascular flow increased 16% for MalPEG-Hb relative to baseline and remained decreased by 44% for SB and 80% for HES. Hemoglobin concentration was 10.4 g/dL with SB, 7.5 (6.8 g/dL in red blood cells and 0.9 g/dL in plasma) with MalPEG-Hb, and 7.5 g/dL with HES, leading to tissue Po(2) of 19, 8, and 5 mm Hg respectively. Calculations of oxygen extraction show that 0.9 g/dL of MalPEG-Hb increased oxygen extraction per gram of red cell hemoglobin in the tissue analyzed compared with SB. These measurements correlate well with a systemic indicator of recovery, base excess, 5.4 +/- 4.7 (MalPEG-Hb), 1.7 +/- 3.8 (SB), and -0.3 +/- 5.7 (HES).

CONCLUSION

The presence of 0.9 g/dL of high oxygen affinity MalPEG-Hb improves microvascular blood flow and oxygen transport during shock to a significantly greater extent than that attainable with blood or HES.

摘要

目的

确定用聚乙二醇修饰的人血红蛋白（MalPEG-Hb）进行复苏是否比自体失血（SB）和5%羟乙基淀粉（HES）更能改善出血后的全身和微血管变量。MalPEG-Hb是一种携氧血液代用品，血红蛋白含量为4 g/dL，粘度为2.5 cP，胶体渗透压为49 mmHg，p50为5.5 mmHg。

设置

实验室。

研究对象

金黄叙利亚仓鼠。

设计

前瞻性研究。

干预措施

对植入皮褶小室的仓鼠进行放血，放血量为血容量的50%，然后用50%的自体失血量（SB、HES或MalPEG-Hb）进行复苏。

测量指标及主要结果

分别监测休克和复苏过程1小时。微血管事件通过血管直径、流速、功能性毛细血管密度以及小动脉、小静脉和血管外组织中的氧分压（Po₂）来表征。全身变量包括平均动脉压、心率、Po₂、Pco₂、pH值和碱剩余。与休克前基线相比，MalPEG-Hb复苏使功能性毛细血管密度增加到64%，而SB为44%，HES为32%。MalPEG-Hb的微血管血流量相对于基线增加了16%，而SB减少了44%，HES减少了80%。SB组血红蛋白浓度为10.4 g/dL，MalPEG-Hb组为7.5（红细胞中6.8 g/dL，血浆中0.9 g/dL），HES组为7.5 g/dL，导致组织Po₂分别为19、8和5 mmHg。氧摄取计算表明，与SB相比，0.9 g/dL的MalPEG-Hb增加了所分析组织中每克红细胞血红蛋白的氧摄取。这些测量结果与恢复的全身指标碱剩余密切相关，分别为5.4±4.7（MalPEG-Hb）、1.7±3.8（SB）和-0.3±5.7（HES）。