氧合血红蛋白血液稀释。氧输送机制及其与一氧化氮供体（硝普钠）的超增强作用。

Rooney M W, Hirsch L J, Mathru M

Department of Anesthesiology, Loyola University Medical Center, Maywood, Illinois 60153.

Anesthesiology. 1993 Jul;79(1):60-72. doi: 10.1097/00000542-199307000-00011.

BACKGROUND

Hemodilution (HD) with oxyhemoglobin colloid (oxyHb) provides a greater arterial oxygen content (CaO2) than HD with conventional colloids; however, oxygen delivery (DO2) is essentially the same, because, in contrast to conventional HD, cardiac output (CO) is not augmented. This study seeks to elucidate the mechanism that limits CO during oxyHb-HD and to test whether infusion of a nitric oxide (NO) donor would augment DO2, because oxyHb is known to inactivate in vitro endothelial-derived NO.

METHODS

Anesthetized dogs were isovolemically hemodiluted with 10% oxyHb, 8% albumin, or 10% methemoglobin (weak NO inactivator) to 20% hematocrit. After HD, sodium nitroprusside (SNP) was titrated intravenously until decreases (> 10 mmHg) in mean aortic pressure (Pao) indicated the presence of exogenous NO. Systemic hemodynamics and regional blood flows (microsphere method) were measured.

RESULTS

Albumin-HD and metHb-HD produced typical HD-mediated responses: increased CO (63-65%), slight decreases (13-15%) in DO2, decreases in systemic vascular resistance (SVR) proportional to the decreases (49-52%) in blood viscosity of all three groups, and increased regional blood flows (RBF). Responses to oxyHb-HD were atypical: CO and its determinants were not changed, DO2 decreased (23%) proportional to CaO2, and SVR and most RBF were not changed except for a net redistribution of CO to myocardium and skeletal muscle. In albumin-HD or metHb-HD, SNP (2-5 micrograms.kg-1.min-1) induced comparable decreases in mean Pao (29-37%) and SVR (39-41%); however, CO, RBF, and DO2 were not affected. In oxyHb-HD, exceptionally large doses of SNP (54 +/- 5 micrograms.kg-1.min-1) decreased mean Pao only 19 +/- 1%; however, CO increased 78 +/- 5% and decreases (61 +/- 3%) in SVR were slightly greater than viscosity reductions. Other determinants of CO were not affected. Most RBF increased proportional to CO; there was, however, preferential distribution to myocardium and skeletal muscle. Consequently, the augmented CO, and CaO2 of oxyHb-HD, produced large increases in DO2, 77 +/- 5% from HD alone and 43 +/- 3% from prehemodilution values.

CONCLUSIONS

This study indicates that the limited CO and DO2 of oxyHb-HD resulted from opposing changes in two determinants of flow, i.e., reduced blood viscosity and increased arterial resistance (vasoconstriction). The vasoconstriction was not evident with metHb-HD and was reversed by the SNP infusion, indicating that oxyHb inactivated in vivo endothelial-derived NO. The ability of the NO donor (SNP) to facilitate large viscosity-mediated increases in DO2 during oxyHb-HD is an important finding that could potentially render oxyHb colloids more useful than conventional colloids, particularly for the individual with a compromised circulation who would benefit from an increased oxygen supply.

背景

与使用传统胶体进行血液稀释（HD）相比，用氧合血红蛋白胶体（oxyHb）进行血液稀释可提供更高的动脉血氧含量（CaO2）；然而，氧输送（DO2）基本相同，因为与传统血液稀释不同，心输出量（CO）并未增加。本研究旨在阐明在oxyHb-HD过程中限制CO的机制，并测试输注一氧化氮（NO）供体是否会增加DO2，因为已知oxyHb在体外会使内皮源性NO失活。

方法

将麻醉的犬等容性地用10% oxyHb、8%白蛋白或10%高铁血红蛋白（弱NO失活剂）进行血液稀释至血细胞比容为20%。血液稀释后，静脉滴定硝普钠（SNP），直至平均主动脉压（Pao）下降（>10 mmHg）表明存在外源性NO。测量全身血流动力学和局部血流量（微球法）。

结果

白蛋白-HD和高铁血红蛋白-HD产生了典型的血液稀释介导的反应：CO增加（63-65%），DO2略有下降（13-15%），全身血管阻力（SVR）下降与三组血液粘度下降（49-52%）成比例，局部血流量（RBF）增加。对oxyHb-HD的反应不典型：CO及其决定因素未改变，DO2与CaO2成比例下降（23%），SVR和大多数RBF未改变，只是CO向心肌和骨骼肌有净重新分布。在白蛋白-HD或高铁血红蛋白-HD中，SNP（2-5微克·千克-1·分钟-1）导致平均Pao有相当程度的下降（29-37%）和SVR下降（39-41%）；然而，CO、RBF和DO2未受影响。在oxyHb-HD中，超大剂量的SNP（54±5微克·千克-1·分钟-1）仅使平均Pao下降19±1%；然而，CO增加78±5%，SVR下降（61±3%）略大于粘度降低。CO的其他决定因素未受影响。大多数RBF与CO成比例增加；然而，存在向心肌和骨骼肌的优先分布。因此，oxyHb-HD增加的CO和CaO2使DO2大幅增加，仅血液稀释时增加77±5%，相对于血液稀释前的值增加43±3%。

结论

本研究表明，oxyHb-HD中有限的CO和DO2是由血流的两个决定因素的相反变化导致的，即血液粘度降低和动脉阻力增加（血管收缩）。高铁血红蛋白-HD时血管收缩不明显，SNP输注可逆转这种情况，表明oxyHb在体内使内皮源性NO失活。NO供体（SNP）在oxyHb-HD期间促进粘度介导的DO2大幅增加的能力是一项重要发现，这可能使oxyHb胶体比传统胶体更有用，特别是对于循环功能受损且将从增加的氧气供应中受益的个体。