Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-2H2]glucose, i.e., D2-glucose, and [3-13C]lactate) techniques involving central venous tracer infusion along with cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Patients with traumatic brain injury (TBI) who had nonpenetrating head injuries (n=12, all male) were entered into the study after consent of patients' legal representatives. Written and informed consent was obtained from healthy controls (n=6, including one female). As in previous investigations, the cerebral metabolic rate (CMR) for glucose was suppressed after TBI. Near normal arterial glucose and lactate levels in patients studied 5.7±2.2 days (range of days 2–10) post-injury, however, belied a 71% increase in systemic lactate production, compared with control, that was largely cleared by greater (hepatic+renal) glucose production. After TBI, gluconeogenesis from lactate clearance accounted for 67.1% of glucose rate of appearance (Ra), which was compared with 15.2% in healthy controls. We conclude that elevations in blood glucose concentration after TBI result from a massive mobilization of lactate from corporeal glycogen reserves. This previously unrecognized mobilization of lactate subserves hepatic and renal gluconeogenesis. As such, a lactate shuttle mechanism indirectly makes substrate available for the body and its essential organs, including the brain, after trauma. In addition, when elevations in arterial lactate concentration occur after TBI, lactate shuttling may provide substrate directly to vital organs of the body, including the injured brain.

我们评估了这样一个假设：受伤大脑的营养需求是通过体内乳酸穿梭的大幅协同增加来支持的。为此，我们使用了双同位素示踪（[6,6 - 2H₂]葡萄糖，即D₂ - 葡萄糖，以及[3 - ¹³C]乳酸）技术，包括中心静脉示踪剂注入以及脑（动脉[art]和颈静脉球[JB]）血液采样。在患者法定代理人同意后，将有非穿透性头部损伤的创伤性脑损伤（TBI）患者（n = 12，均为男性）纳入研究。从健康对照组（n = 6，包括1名女性）获得了书面知情同意书。与先前的研究一样，TBI后葡萄糖的脑代谢率（CMR）受到抑制。然而，在受伤后5.7±2.2天（2 - 10天范围）研究的患者中，接近正常的动脉葡萄糖和乳酸水平掩盖了与对照组相比全身乳酸产生增加71%的情况，这主要通过更高的（肝 + 肾）葡萄糖产生来清除。TBI后，乳酸清除产生的糖异生占葡萄糖出现率（Ra）的67.1%，而在健康对照组中这一比例为15.2%。我们得出结论，TBI后血糖浓度升高是由于身体糖原储备中乳酸的大量动员所致。这种先前未被认识到的乳酸动员有助于肝脏和肾脏的糖异生。因此，乳酸穿梭机制在创伤后间接为身体及其重要器官（包括大脑）提供底物。此外，当TBI后动脉乳酸浓度升高时，乳酸穿梭可能直接为身体的重要器官（包括受伤的大脑）提供底物。