Lactate, not glucose, up-regulates mitochondrial oxygen consumption both in sham and lateral fluid percussed rat brains

OBJECTIVE: Failure of energy metabolism after traumatic brain injury may be a major factor limiting outcome. Although glucose is the primary metabolic substrate in the healthy brain, the well documented surge in tissue lactate after traumatic brain injury suggests that lactate may provide an energy need that cannot be met by glucose. We hypothesized, therefore, that administration of lactate or the combination of lactate and supraphysiological oxygen may improve mitochondrial oxidative respiration in the brain after rat fluid percussion injury. We measured oxygen consumption (VO2) to determine what effects glucose, lactate, oxygen, and the combination of lactate and oxygen have on mitochondrial respiration in both injured and uninjured rat brain tissue. METHODS: Anesthetized Sprague-Dawley rats were intubated and ventilated with either 0.21 or 1.0 fraction of inspired oxygen (FIO2). Brain tissue from acute sham animals was subjected in vitro to 1.1 mM, 12 mM and 100 mM concentrations of glucose and L-lactate. In another group, injury (fluid percussion injury of 2.5 +/- 0.02 atmospheres) was induced over the left hemisphere. The VO2 of mug amounts of brain tissues were measured in a microrespirometry system (Cartesian diver). RESULTS: The VO2 was found to be independent of glucose concentrations, but dose-dependent for lactate. Moreover, the lactate dependent VO2s were all significantly higher than those generated by glucose. Injured rats on FIO2 0.21 had brain tissue VO2 rates that were significantly lower than those of shams or preinjury levels. In injured rats treated with FIO2 1.0, the reduction in VO2 levels was prevented. Injured rats that received an intravenous infusion of 100 mM lactate had VO2 rates that were significantly higher than those obtained with FIO2 1.0. Combined treatment further boosted the lactate generated VO2 rates by approximately 15%. CONCLUSION: Glucose sustains mitochondrial respiration at a low level "fixed" rate because, despite increasing its concentration nearly 100-fold, it cannot up-regulate VO2 after fluid percussion injury. Lactate produces a dose-dependent VO2 response, possibly enabling mitochondria to meet the increased energy needs of the injured brain.

Arterio-venous gradients of free energy change for assessment of systemic and splanchnic perfusion in cardiac surgery patients

OBJECTIVE: Adequacy of organ perfusion depends on sufficient oxygen supply in relation to the metabolic needs. The aim of this study was to evaluate the relationship between gradients of free energy change, and the more commonly used parameter for the evaluation of the adequacy of organ perfusion, such as oxygen-extraction in patients undergoing valve replacement surgery using normothermic cardiopulmonary bypass (CPB). METHODS: In 43 cardiac patients, arterial, mixed venous, and hepato-venous blood samples were taken synchronously after induction of anaesthesia (preCPB), during CPB, and 2 and 7 h after admission to the intensive care unit (ICU+2, ICU+7). Blood gas analysis, cardiac output, and hepato-splanchnic blood flow were measured. Free energy change gradients between mixed venous and arterial (-deltadeltaG(v - a)) and hepato-venous and arterial (-deltadeltaG(hv - a)) compartments were calculated. MEASUREMENTS AND RESULTS: Cardiac index (CI) increased from 1.9 (0.7) to 2.8 (1.3) L/min/m (median, inter-quartile range) (p = 0.001), and hepato-splanchnic blood flow index (HBFI) from 0.6 (0.22) to 0.8 (0.53) L/min/m (p = 0.001). Despite increasing flow, systemic oxygen extraction increased after CPB from 24 (10)% to 35 (10)% at ICU+2 (p = 0.002), and splanchnic oxygen extraction increased during CPB from 37 (19)% to 52 (14)% (p = 0.001), and remained high thereafter. After CPB, high splanchnic and systemic gradients of free energy change gradients were associated with high splanchnic and systemic oxygen extraction, respectively (p = 0.001, 0.033, respectively). CONCLUSION: Gradients of free energy change may be helpful in characterising adequacy of perfusion in cardiac surgery patients independently from measurements or calculations of data from oxygen transport.

Negotiating an Energy Deal under TTIP: Drivers and Impediments to U.S. Shale Exports to Europe

The problem of global security of energy supply is growing in importance. TTIP negotiations represent an opportunity to improve energy security in Europe and negotiate a legal framework for bilateral trade in energy, which could serve as a model for future negotiations at a multilateral level. This paper explores some of the thorniest legal, geopolitical, and economic issues that need to be taken up by TTIP negotiators for the promotion of a secure and sustainable trade in energy between the United States and European Union. It gives an account of the most recent developments in the TTIP negotiations on energy and examines the link between a possible legal framework for energy trade under TTIP and other energy-related regional and international fora. The paper critically assesses the negotiating positions of the European Union and the United States in light of their reciprocal energy profiles and needs. It offers an overview of the critical items most likely to be on top of the TTIP agenda on energy based on a comparative analysis of energy provisions in E.U. and U.S. legislation and in light of the both parties’ interests. Finally, it discusses the main driving forces and inhibiting factors capable of facilitating or rather impeding a successful conclusion of an energy trade deal between the United States and the European Union.