Lactate in the intensive care unit: pyromaniac, sentinel or fireman?

Lactate, indispensable substrate of mammalian intermediary metabolism, allows shuttling of carbons and reducing power between cells and organs at a high turnover rate. Lactate is, therefore, not deleterious, although an increase in its concentration is often a sensitive sign of alteration in energy homeostasis, a rise in it being frequently related to poor prognosis. Such an increase, however, actually signifies an attempt by the body to cope with a new energy status. Hyperlactatemia, therefore, most often represents an adaptive response to an acute energy disorder. Investigation of lactate metabolism at the bedside is limited to the determination of its concentration. Lactate metabolism and acid-base homeostasis are both closely linked to cellular energy metabolism, acidosis being potentially a cause or a consequence of cellular energy deficit

Lactate: A key metabolite in the intercellular metabolic interplay

Most physicians involved in intensive care consider lactate solely as a deleterious metabolite, responsible for high morbidity and bad prognosis in severe patients. For the physiologist, however, lactate is a key metabolite, alternatively produced or consumed. Many studies in the literature have infused animals or humans with exogenous lactate, demonstrating its safety and usefulness, but the bad reputation of lactate is still widespread. The metabolic meaning of glucose–lactate cycling exceeds its initial role described by Cori and Cori. According to recent works concerning lactate, it can be predicted that a new role as a therapeutic agent will arise for this metabolite

The Lactate/Pyruvate Ratio of Metabolic Modulation Using Glucose Insulin Kalium and Lactate Solution and Their Effect on Functional Mechanical Recovery of the Isolated Perfused Heart

Metabolic modulation with Glucose Insulin Kalium (GIK) solution has beenreally well known in their capacity to improve post ischemic heart function. In this regardGIK intervention on post operative Coronary Artery Bypass Graft (CABG) can improveheart function recovery on reperfusion period (Goldhaber dan Weiss, 1992; Atwell et al.,1997). Post operative CABG intervention with GIK will produce a beneficial effect onthe elevation of heart energy to prevent ionic homeostasis disturbance and reactiveoxygen species (ROS) production that become the basis of reperfusion injury (Silvermandan Stern, 1994; Cross et al., 1995; Taegtmeyer et al., 1997; Opie, 1999; Lazar, 2002;Doenst et al., 2003; Trence et al., 2003).Many efforts have been made to clarify how exactly GIK works to improve postischemic heart function as in CABG. This is crucially done in order to be able to modifythe solution concerned. Although this solution has been clearly proved to improve postischemic heart function, it is not totally free from its adverse effect. Its main side effect isthat it can provoke hyperglycemic state, which contrasts with the tight glucose control incontinuously normal range for the patients who are critically ill.In this study lactate and pyruvate level in the coronary effluent were measuredfrom the isolated heart directly perfused with GIK and lactate. It was shown that thepreischemic lactate level was low and then clearly elevated as soon as the reperfusiontook place due to anaerobic metabolism. In accordance with reperfusion time lactate leveldecreased gradually. In relation with pyruvate level, this substrate evolution looked likethe appearance of lactate but its value was lower if compared with lactate.The recovery in functional mechanical activity of the post ischemic heart seems tobe much more related to the pattern of the evolution of logarithmic lactate/pyruvate ratio(L/P ratio). Logarithmic value of L/P ratio in GIK group increased since the earlyreperfusion period (+40%, p < 0.05), followed by improvement in recovery ofmechanical activity in this group which was significantly higher if compared with thecontrol group. Similar fashion was found in lactate group in regard to the evolution of thelogarithmic value of L/P ratio in this group, where its value was significantly highercompared with the control group. The logarithmic evolution pattern on L/P ratio for thisgroup increased along the reperfusion time (+34% p < 0.05).From the present study, it can be concluded that the recovery of functionalmechanical activity of the post ischemic heart perfused with GIK is through modificationon cellular lactate metabolism

The Lactate/Pyruvate Ratio of Metabolic Modulation using Glucose Insulin Kalium and Lactate Solution and their Effect on Functional Mechanical Recovery of the Isolated Perfused Heart

Metabolic modulation with Glucose Insulin Kalium (GIK) solution has beenreally well known in their capacity to improve post ischemic heart function. In this regardGIK intervention on post operative Coronary Artery Bypass Graft (CABG) can improveheart function recovery on reperfusion period (Goldhaber dan Weiss, 1992; Atwell et al.,1997). Post operative CABG intervention with GIK will produce a beneficial effect onthe elevation of heart energy to prevent ionic homeostasis disturbance and reactiveoxygen species (ROS) production that become the basis of reperfusion injury (Silvermandan Stern, 1994; Cross et al., 1995; Taegtmeyer et al., 1997; Opie, 1999; Lazar, 2002;Doenst et al., 2003; Trence et al., 2003).Many efforts have been made to clarify how exactly GIK works to improve postischemic heart function as in CABG. This is crucially done in order to be able to modifythe solution concerned. Although this solution has been clearly proved to improve postischemic heart function, it is not totally free from its adverse effect. Its main side effect isthat it can provoke hyperglycemic state, which contrasts with the tight glucose control incontinuously normal range for the patients who are critically ill.In this study lactate and pyruvate level in the coronary effluent were measuredfrom the isolated heart directly perfused with GIK and lactate. It was shown that thepreischemic lactate level was low and then clearly elevated as soon as the reperfusiontook place due to anaerobic metabolism. In accordance with reperfusion time lactate leveldecreased gradually. In relation with pyruvate level, this substrate evolution looked likethe appearance of lactate but its value was lower if compared with lactate.The recovery in functional mechanical activity of the post ischemic heart seems tobe much more related to the pattern of the evolution of logarithmic lactate/pyruvate ratio(L/P ratio). Logarithmic value of L/P ratio in GIK group increased since the earlyreperfusion period (+40%, p < 0.05), followed by improvement in recovery ofmechanical activity in this group which was significantly higher if compared with thecontrol group. Similar fashion was found in lactate group in regard to the evolution of thelogarithmic value of L/P ratio in this group, where its value was significantly highercompared with the control group. The logarithmic evolution pattern on L/P ratio for thisgroup increased along the reperfusion time (+34% p < 0.05).From the present study, it can be concluded that the recovery of functionalmechanical activity of the post ischemic heart perfused with GIK is through modificationon cellular lactate metabolism

Ubiquinone Analogs: A Mitochondrial Permeability Transition Pore-Dependent Pathway to Selective Cell Death

International audienceBACKGROUND: Prolonged opening of the mitochondrial permeability transition pore (PTP) leads to cell death. Various ubiquinone analogs have been shown to regulate PTP opening but the outcome of PTP regulation by ubiquinone analogs on cell fate has not been studied yet. METHODOLOGY/PRINCIPAL FINDINGS: The effects of ubiquinone 0 (Ub(0)), ubiquinone 5 (Ub(5)), ubiquinone 10 (Ub(10)) and decyl-ubiquinone (DUb) were studied in freshly isolated rat hepatocytes, cultured rat liver Clone-9 cells and cancerous rat liver MH1C1 cells. PTP regulation by ubiquinones differed significantly in permeabilized Clone-9 and MH1C1 cells from that previously reported in liver mitochondria. Ub(0) inhibited PTP opening in isolated hepatocytes and Clone-9 cells, whereas it induced PTP opening in MH1C1 cells. Ub(5) did not affect PTP opening in isolated hepatocytes and MH1C1 cells, but it induced PTP opening in Clone-9 cells. Ub(10) regulated PTP in isolated hepatocytes, whereas it did not affect PTP opening in Clone-9 and MH1C1 cells. Only DUb displayed the same effect on PTP regulation in the three hepatocyte lines tested. Despite such modifications in PTP regulation, competition between ubiquinones still occurred in Clone-9 and MH1C1 cells. As expected, Ub(5) induced a PTP-dependent cell death in Clone-9, while it did not affect MH1C1 cell viability. Ub(0) induced a PTP-dependent cell death in MH1C1 cells, but was also slightly cytotoxic in Clone-9 by an oxidative stress-dependent mechanism. CONCLUSIONS/SIGNIFICANCE: We found that various ubiquinone analogs regulate PTP in different ways depending on the cell studied. We took advantage of this unique property to develop a PTP opening-targeted strategy that leads to cell death specifically in cells where the ubiquinone analog used induces PTP opening, while sparing the cells in which it does not induce PTP opening

Qualité des aliments, qualité de l’alimentation

Introduction Comme chaque mammifère, l’Homme est caractérisé par l’existence de besoins nutritionnels élevés, indispensables pour satisfaire aux différentes fonctions qu’impliquent sa physiologie et son mode de vie. Ces besoins sont couverts à partir de différents constituants prélevés dans le milieu extérieur sous forme d’aliments, d’eau et d’oxygène. Cela est assuré par les fonctions métaboliques et de respiration. Selon leur devenir, on peut classer ces différents éléments en deux groupes ..

Mitochondrial function and substrate availability.

International audienceCarbohydrates and lipid oxidations support energy metabolism by distinct pathways exhibiting similarities and differences. Alterations of energy metabolism during sepsis are well recognized; however, failure of oxygen or substrate supply is not a prominent cause. The occurrence of a "mitochondrial cytopathy" induced by sepsis explains some of these abnormalities, which may represent a "metabolic hibernation," a potential strategy of defense during the very acute phase of the illness. Our view of the involvement of mitochondrial metabolism in cell signaling has evolved considerably. Because of the structure of the respiratory chain, the way electrons are provided (upstream or downstream of complex 1 [i.e., nicotinamide adenine dinucleotide {reduced form} or flavin adenine dinucleotide {reduced form}]) plays an important role in the regulation of several functions, including the yield of adenosine triphosphate synthesis and the production of reactive oxygen species. Moreover, the modern view of energy channeling and compartmentation in the cell may open attractive hypotheses regarding the changes in cellular energy distribution in pathologic states, such as sepsis