Haouzi Philippe, Van de Louw Andry
Pennsylvania State University, College of Medicine, Division of Pulmonary and Critical Care Medicine, Penn State Hershey Medical Center, 500 University Dr., Hershey, PO Box 850, Hershey, PA 17033, USA.
Pennsylvania State University, College of Medicine, Division of Pulmonary and Critical Care Medicine, Penn State Hershey Medical Center, 500 University Dr., Hershey, PO Box 850, Hershey, PA 17033, USA.
Respir Physiol Neurobiol. 2015 Aug 15;215:39-46. doi: 10.1016/j.resp.2015.04.009. Epub 2015 Apr 21.
Our study intended to determine the effects on oxygen uptake (VO2) of restoring a normal rate of O2 delivery following blood transfusion (BT) after a severe hemorrhage (H). Spontaneously breathing urethane anesthetized rats were bled by removing 20 ml/kg of blood over 30 min. Rats were then infused with their own shed blood 15 min after the end of H. At mid-perfusion, half of the rats received a unique infusion of the decoupling agent 2,4-dinitrophenol (DNP, 6 mg/kg). VO2 and arterial blood pressure (ABP) were continuously measured throughout the study, along with serial determination of blood lactate concentration [La]. Animals were euthanized 45 min after the end of reperfusion; liver and lungs were further analyzed for early expression of oxidative stress gene using RT-PCR. Our bleeding protocol induced a significant decrease in ABP and increase in [La], while VO2 dropped by half. The O2 deficit progressively accumulated during the period of bleeding reached -114 ± 53 ml/kg, just before blood transfusion. Despite the transfusion of blood, a significant O2 deficit persisted (-82 ± 59 ml/kg) 45 min after reperfusion. This slow recovery of VO2 was sped up by DNP injection, leading to a fast recovery of O2 deficit after reperfusion, becoming positive (+460 ± 132 ml/kg) by the end of the protocol, supporting the view that O2 supply is not the main controller of VO2 dynamics after BT. Of note is that DNP also enhanced oxidative stress gene expression (up-regulation of NADPH oxidase 4 in the lung for instance). The mechanism of slow recovery of O2 requirement/demand following BT and the resulting effects on tissues exposed to relatively high O2 partial pressure are discussed.
我们的研究旨在确定严重出血（H）后输血（BT）恢复正常氧输送速率对氧摄取（VO2）的影响。将自发呼吸的氨基甲酸乙酯麻醉大鼠在30分钟内放血20 ml/kg。放血结束后15分钟，给大鼠输注自身流失的血液。在灌注中期，一半的大鼠接受一次解偶联剂2,4-二硝基苯酚（DNP，6 mg/kg）输注。在整个研究过程中持续测量VO2和动脉血压（ABP），并连续测定血乳酸浓度[La]。再灌注结束后45分钟对动物实施安乐死；使用逆转录聚合酶链反应（RT-PCR）进一步分析肝脏和肺组织中氧化应激基因的早期表达。我们的放血方案导致ABP显著降低，[La]升高，而VO2下降了一半。在放血期间，氧亏缺逐渐累积，在输血前达到-114±53 ml/kg。尽管进行了输血，但再灌注45分钟后仍存在显著的氧亏缺（-82±59 ml/kg）。DNP注射加快了VO2的缓慢恢复，导致再灌注后氧亏缺快速恢复，在实验结束时变为正值（+460±132 ml/kg），支持了氧供应不是BT后VO2动力学主要控制因素的观点。值得注意的是，DNP还增强了氧化应激基因表达（例如肺中NADPH氧化酶4上调）。本文讨论了BT后氧需求恢复缓慢的机制以及由此对暴露于相对高氧分压的组织产生的影响。
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