Curtis S E, Cain S M
Department of Pediatrics, University of Alabama, Birmingham 35294.
Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):348-54. doi: 10.1164/ajrccm/145.2_Pt_1.348.
Pathologic oxygen supply dependency (PO2SD) may be etiologic in multisystem organ failure (MSOF) and has been related to mortality in sepsis. Although elevated lactate levels are generally assumed to be a marker of anaerobiosis in these patients, endotoxin may increase serum lactate by inactivation of pyruvate dehydrogenase (PDH), unrelated to tissue PO2. We hypothesized that regional lactate flux may correlate poorly with local oxygen delivery in sepsis. This study examined both the whole-body (WB) and regional (isolated hind limb L and gut G) responses to endotoxin infusion in terms of oxygen delivery, oxygen uptake, and lactate flux in 12 pentobarbital-anesthetized dogs. To separate hypoxia-induced lactate production from that related to inactivation of PDH by endotoxin, half the dogs received dichloroacetate (DCA), a PDH activator. After endotoxin and volume resuscitation, each animal had low systemic vascular resistance with normal to high cardiac output. Despite adequate oxygen delivery to WB, L, and G, arterial lactate levels rose significantly. A 30-min hypoxic challenge (12% FIO2) did not increase lactate levels but did increase WB O2 uptake. DCA normalized lactate levels without influencing oxygen delivery and uptake relations. These data show that lactate levels in endotoxic states may be a poor marker of tissue hypoxia and may be more related to PDH activity.
病理性氧供依赖（PO2SD）可能是多系统器官衰竭（MSOF）的病因，并且与脓毒症的死亡率相关。尽管通常认为这些患者中乳酸水平升高是无氧代谢的标志，但内毒素可能通过丙酮酸脱氢酶（PDH）失活而增加血清乳酸水平，这与组织氧分压无关。我们推测在脓毒症中局部乳酸通量与局部氧输送可能相关性较差。本研究在12只戊巴比妥麻醉的犬中，从氧输送、氧摄取和乳酸通量方面检查了对内毒素输注的全身（WB）和局部（分离的后肢L和肠道G）反应。为了将缺氧诱导的乳酸生成与内毒素导致的PDH失活相关的乳酸生成区分开来，一半的犬接受了二氯乙酸（DCA），一种PDH激活剂。在内毒素和容量复苏后，每只动物的体循环血管阻力较低，心输出量正常至高。尽管向WB、L和G提供了充足的氧输送，但动脉乳酸水平仍显著升高。30分钟的低氧刺激（12% FIO2）并未增加乳酸水平，但确实增加了WB的氧摄取。DCA使乳酸水平正常化，而不影响氧输送和摄取关系。这些数据表明，内毒素状态下的乳酸水平可能不是组织缺氧的良好标志，可能与PDH活性更相关。
