Driessen B, Jahr J S, Lurie F, Gunther R A
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348, USA.
J Vet Pharmacol Ther. 2001 Feb;24(1):61-71. doi: 10.1046/j.1365-2885.2001.00307.x.
Stroma-free hemoglobin-based oxygen carriers (HBOC) have been developed to overcome problems associated with transfusion of allogeneic blood. We have studied the efficacy of the first licensed veterinary blood substitute, hemoglobin glutamer-200 bovine (Oxyglobin; Biopure, Cambridge, MA, USA, Hb-200), in a canine model of acute hypovolemia and examined whether clinically commonly used criteria are adequate to guide fluid resuscitation with this product. Twelve anesthetized dogs were instrumented for measurements of physiological variables including hemodynamic, oxygenation, and blood gas and acid-base parameters. Dogs were bled to a mean arterial pressure (MAP) of 50 mmHg for 1 h followed by resuscitation with either shed blood (controls) or Hb-200 until heart rate (HR), MAP and central venous pressure (CVP) returned to baseline. Recordings were repeated immediately and 3 h after termination of fluid resuscitation. Hemorrhage (average 32 mL/kg) caused significant decreases in total hemoglobin (Hb), mean pulmonary arterial pressure (PAP), cardiac output (CO) and oxygen delivery (DO2I), increases in HR and systemic vascular resistance (SVRI), and lactic acidosis. In controls, only re-transfusion of all shed blood returned HR, MAP and CVP to prehemorrhage values, whereas in other dogs this endpoint was reached with infusion of 10 mL/kg Hb-200. Unlike blood transfusion, Hb-200 infusion failed to return CI and DO2I to baseline and to increase arterial oxygen content (CaO2) and total Hb; SVRI further increased. Thus, commonly used criteria (HR, MAP, CVP) to guide transfusion therapy in patients posthemorrhage prove insufficient when HBOCs with pronounced vasoconstrictive action are used and lead to inadequate volume repletion.
无基质血红蛋白氧载体（HBOC）已被研发出来，以克服与异体输血相关的问题。我们研究了首个获得许可的兽用血液替代品——血红蛋白谷氨酰胺-200牛（Oxyglobin；美国马萨诸塞州剑桥市Biopure公司，Hb-200）在犬急性低血容量模型中的疗效，并探讨了临床常用标准是否足以指导该产品的液体复苏。对12只麻醉犬进行仪器安装，以测量包括血流动力学、氧合以及血气和酸碱参数在内的生理变量。将犬放血至平均动脉压（MAP）为50 mmHg，持续1小时，随后用自体失血（对照组）或Hb-200进行复苏，直至心率（HR）、MAP和中心静脉压（CVP）恢复至基线水平。在液体复苏结束后立即及3小时重复记录。出血（平均32 mL/kg）导致总血红蛋白（Hb）、平均肺动脉压（PAP）、心输出量（CO）和氧输送（DO2I）显著降低，HR和全身血管阻力（SVRI）增加，以及乳酸酸中毒。在对照组中，仅回输所有失血量可使HR、MAP和CVP恢复至出血前值，而在其他犬中，输注10 mL/kg Hb-200即可达到该终点。与输血不同，输注Hb-200未能使心脏指数（CI）和DO2I恢复至基线水平，也未能增加动脉血氧含量（CaO2）和总Hb；SVRI进一步升高。因此，当使用具有明显血管收缩作用的HBOC时，用于指导出血后患者输血治疗的常用标准（HR、MAP、CVP）被证明是不足的，并且会导致容量补充不足。
