Abstract 10941: Cerebral Consumption of Lactate Increases Neurological Injury After Experimental Cardiac Arrest in Rabbits

Introduction: Neuronal consumption of lactate is known to be protective after long duration of brain ischaemia. However, its consequences on neurological function after shorter duration of ischemia like after cardiac arrest are unknown. Hypothesis: We hypothesized that cerebral lactate consumption is deleterious for neurological outcome, whereas lactate dehydrogenase inhibition by oxamate could improve recovery. Methods: Male New-Zealand rabbits were anesthetized and surgically instrumented to assess lactate, glucose and O 2 cerebral consumption by measurement of the arterio-jugular differences. After 10 min of ventricular fibrillation, animals were resuscitated and randomly received a 30-min infusion of either saline (Control, n=6), lactate (Lact, 5 mg/kg/min, n=6) or oxamate (Oxa, 37.5 mg/kg/min, n=6). They were followed during 4 h. Additional animals were submitted to the same procedure without surgical instrumentation to allow recovery and assessment of neurological function during 48 h after cardiac arrest. In both experiments, neuronal death was assessed histologically by fluorojade C staining. Results: In Control group, a strong increase of the cerebral consumption of O 2 , glucose and lactate was observed during the 4 hours following resuscitation. In Lact group, lactate consumption was increased as compared to Control, whereas it was almost abolished in Oxa group (17.13±3.59, 32.60±6.24 and 4.04±1.58 mmol/L/min in Control, Lact and Oxa, respectively). Additionally, Oxa group presented a reduced consumption of glucose and O 2 after cardiac arrest as compared to other groups. Interestingly, administration of oxamate was highly neuroprotective whereas lactate administration worsened the neurological outcome after cardiac arrest (38±4, 64±10 and 15±6 % of neurological dysfunction score at 48h in Control, Lact and Oxa, respectively). Oxamate infusion was also associated with a significant reduction in the number of degenerative neurons at 4 h and 48 h of follow-up. Conclusions: The cerebral consumption of lactate appeared to be detrimental in rabbits after cardiac arrest. Its inhibition by oxamate is potently neuroprotective.

Lactate Metabolism and Microbiome Composition Are Affected by Nitrogen Gas Supply in Continuous Lactate-Based Chain Elongation

Chain elongation reactor microbiomes produce valuable medium-chain carboxylates (MCC) from non-sterile residual substrates where lactate is a relevant intermediate. Gas supply has been shown to impact chain elongation performance. In the present study, the effect of nitrogen gas (N2) supply on lactate metabolism, conversion rates, biomass growth, and microbiome composition was evaluated in a lactate-fed upflow anaerobic reactor with continuous or intermittent N2 gas supply. Successful MCC production was achieved with continuous N2 gas supply at low superficial gas velocities (SGV) of 0.22 m∙h−1. Supplying N2 at high SGV (>2 m∙h−1) either continuously (2.2 m∙h−1) or intermittently (3.6 m∙h−1) disrupted chain elongation, resulting in production of short-chain carboxylates (SCC), i.e., acetate, propionate, and n-butyrate. Caproiciproducens-dominated chain-elongating microbiomes enriched at low SGV were washed out at high SGV where Clostridium tyrobutyricum-dominated microbiomes thrived, by displaying higher lactate consumption rates. Suspended growth seemed to be dominant regardless of SGV and gas supply regime applied with no measurable sludge bed formed. The highest MCC production from lactate of 10 g COD∙L−1∙d−1 with electron selectivities of 72 ± 5%was obtained without N2 gas supply at a hydraulic retention time (HRT) of 1 day. The addition of 5 g∙L−1 of propionate did not inhibit chain elongation, but rather boosted lactate conversion rates towards MCC with n-heptylate reaching 1.8 g COD∙L−1∙d−1. N2 gas supply can be used for mixing purposes and to steer lactate metabolism to MCC or SCC production.

Lactate as substrate for mitochondrial respiration in alveolar epithelial type II cells

Because of the many energy-demanding functions they perform and their physical location in the lung, alveolar epithelial type II (ATII) cells have a rapid cellular metabolism and the potential to influence substrate availability and bioenergetics both locally in the lung and throughout the body. A thorough understanding of ATII cell metabolic function in the healthy lung is necessary for determining how metabolic changes may contribute to pulmonary disease pathogenesis; however, lung metabolism is poorly understood at the cellular level. Here, we examine lactate utilization by primary ATII cells and the ATII model cell line, MLE-15, and link lactate consumption directly to mitochondrial ATP generation. ATII cells cultured in lactate undergo mitochondrial respiration at near-maximal levels, two times the rates of those grown in glucose, and oxygen consumption under these conditions is directly linked to mitochondrial ATP generation. When both lactate and glucose are available as metabolic substrate, the presence of lactate alters glucose metabolism in ATII to favor reduced glycolytic function in a dose-dependent manner, suggesting that lactate is used in addition to glucose when both substrates are available. Lactate use by ATII mitochondria is dependent on monocarboxylate transporter (MCT)-mediated import, and ATII cells express MCT1, the isoform that mediates lactate import by cells in other lactate-consuming tissues. The balance of lactate production and consumption may play an important role in the maintenance of healthy lung homeostasis, whereas disruption of lactate consumption by factors that impair mitochondrial metabolism, such as hypoxia, may contribute to lactic acid build-up in disease.