Eldridge J, Russell R, Christenson R, Sakamoto R, Williams J, Parr M, Trump B, Delaney P, Mackenzie C F
Department of Anesthesiology, University of Maryland, School of Medicine, Baltimore, USA.
Crit Care Med. 1996 Apr;24(4):663-71. doi: 10.1097/00003246-199604000-00019.
To test the effects of three hemoglobin solutions on liver function and hepatic morphology after resuscitation from severe hemorrhagic shock.
Prospective study.
Laboratory.
Thirty-three beagle dogs.
Hemorrhagic shock was induced in anesthetized dogs by removal of blood at a rate of 2 mL/kg/min until systolic blood pressure (BP) reached 50 mm Hg. BP was maintained at this level 2 hrs by further withdrawing 5 to 10 mL aliquots whenever BP increased > 50 mm Hg. Resuscitation was then initiated with autologous whole blood (n = 7), 4% pyridoxalated-hemoglobin-polyoxyethylene conjugate (4% PHP [n = 6]), 8% pyridoxalated-hemoglobin-polyoxyethylene conjugate (8% PHP [n = 9], or 8% stroma-free hemoglobin (n = 7). Four dogs were managed identically but were not resuscitated. Gross necropsy and histologic examination of the liver were performed on all dogs after 7 days, or earlier if death occurred.
In vitro interferences of PHP and stroma-free hemoglobin with liver function tests were determined and recommendations for interpretation of results from blood samples containing PHP and stroma-free hemoglobin were made. Blood was collected before, during, and after resuscitation from hemorrhagic shock. The dogs were then awakened and survivors were monitored daily with blood sampling until they were killed and necropsy was performed. After 7 days, the survival rate following hemorrhagic shock was 100% for whole blood and 4% PHP, 86% for stroma-free hemoglobin, and 33% for 8% PHP. Of the resuscitated dogs not surviving 7 days, all but one died within 27 hrs from coagulopathy. All dogs not resuscitated died within 1.75 hrs after 2 hrs of shock. Bilirubin, alkaline phosphatase, and lactic dehydrogenase concentrations could not be measured due to interferences of stroma-free hemoglobin and PHP. Aspartate (AST) and alanine (ALT) aminotransferase concentrations could be measured after dilution to overcome the interferences. Significant increases in AST and ALT values in all groups 24 hrs after resuscitation were attributed to hypoxic hepatocellular damage associated with the severity of the shock model rather than to the resuscitation fluid. Liver histology showed no changes attributed to toxic damage of hepatocytes in dogs resuscitated with stroma-free hemoglobin or PHP. However, changes, were less severe in dogs resuscitated with 4% PHP than in other groups.
Morphologic studies at necropsy and liver function tests in dogs receiving hemoglobin solutions, compared with autologous blood, support the conclusion that the PHP and stroma-free hemoglobin solutions tested did not produce hepatic toxicity when used as resuscitation fluids in this model of severe shock.
测试三种血红蛋白溶液对严重失血性休克复苏后肝功能和肝脏形态的影响。
前瞻性研究。
实验室。
33只比格犬。
对麻醉的犬只以2 mL/kg/min的速率采血诱导失血性休克，直至收缩压（BP）达到50 mmHg。每当BP升高超过50 mmHg时，通过进一步抽取5至10 mL等分血液将BP维持在此水平2小时。然后用自体全血（n = 7）、4%吡哆醛化血红蛋白-聚氧乙烯共轭物（4% PHP [n = 6]）、8%吡哆醛化血红蛋白-聚氧乙烯共轭物（8% PHP [n = 9]）或8%无基质血红蛋白（n = 7）进行复苏。四只犬只接受相同处理但未进行复苏。7天后对所有犬只进行肝脏大体尸检和组织学检查，若死亡则提前进行。
确定了PHP和无基质血红蛋白对肝功能测试的体外干扰，并对含PHP和无基质血红蛋白的血样结果解读提出建议。在失血性休克复苏前、期间和之后采集血液。然后唤醒犬只，对存活者每天进行血样采集监测，直至处死并进行尸检。7天后，全血和4% PHP复苏后失血性休克的存活率为100%，无基质血红蛋白为86%，8% PHP为33%。在未存活7天的复苏犬只中，除一只外，均在27小时内死于凝血病。所有未复苏的犬只在休克2小时后1.75小时内死亡。由于无基质血红蛋白和PHP的干扰，无法测量胆红素、碱性磷酸酶和乳酸脱氢酶浓度。稀释后可测量天冬氨酸（AST）和丙氨酸（ALT）转氨酶浓度以克服干扰。复苏后24小时所有组中AST和ALT值显著升高归因于与休克模型严重程度相关的缺氧性肝细胞损伤，而非复苏液。肝脏组织学显示，用无基质血红蛋白或PHP复苏的犬只中，未发现归因于肝细胞毒性损伤的变化。然而，用4% PHP复苏的犬只变化比其他组轻。
与自体血液相比，接受血红蛋白溶液的犬只尸检时的形态学研究和肝功能测试支持以下结论：在该严重休克模型中用作复苏液时，所测试的PHP和无基质血红蛋白溶液不会产生肝毒性。
