Évaluation du lactate sanguin chez les chiens atteints de cancer

Malgré le manque d’études sur ce sujet, le cancer est considéré comme une des principales causes d’hyperlactatémie de type B chez le chien. Les cellules malignes ont une production accrue de lactates secondaire à une glycolyse aérobie accrue, via l’effet Warburg. Les mécanismes ne sont pas encore clairement établis mais certains auteurs suggèrent que le cancer pourrait causer une hyperlactatémie via l’effet Warburg. Cette étude a pour objectif de déterminer si les tumeurs malignes peuvent être associées à une hyperlactatémie cliniquement significative (≥2,5 mmol/L) chez le chien. Trente-sept chiens atteints de tumeurs malignes ont été recrutés (22 atteints de tumeurs hématopoïétiques et 15 de tumeurs non hématopoïétiques). Le diagnostic était confirmé par analyse histologique, ou cytologique en cas de lymphome. Les autres causes possibles d’hyperlactatémie étaient écartées puis la mesure des lactates sanguins était réalisée sur sang veineux jugulaire immédiatement analysé avec le LactatePro®. Aucun chien n’était hyperlactatémique. La concentration moyenne en lactates sanguins était de 1,09 mmol/L. La concentration moyenne en lactates sanguins pour les chiens atteints de tumeurs non hématopoïétiques et hématopoïétiques était respectivement de 0,95 mmol/L et de 1,19 mmol/L. Les chiens atteints de lymphome (n=18) avaient une concentration moyenne en lactates sanguins de 1,15 mmol/L. Les tumeurs malignes ne sont pas associées à une hyperlactatémie de type B cliniquement significative chez le chien. L’hyperlactatémie tumorale est donc une complication rare chez le chien. Son diagnostic devrait conduire à une investigation minutieuse des autres causes d’hyperlactatémie.

Coût bioenergetique des modes de déplacements irréguliers en sport

The objective of this thesis was to quantify the physiological responses such as O2 uptake (VO2), heart rate (HR) and blood lactate ([LA]) to some types of activities associated with intermittent sports in athletes. Our hypothesis is that the introduction of accelerations and decelerations with or without directional changes results in a significative increase of the oxygen consumption, heart rate and blood lactate. The purpose of the first study was to measure and compare the VO2 and the HR of 6 on-court tennis drills at both high and low displacement speeds. These drills were done with and without striking the ball, over full and half-width court, in attack or in defense mode, using backhand or forehand strokes. Results show that playing an attacking style requires 6.5% more energy than playing a defensive style (p < 0.01) and the backhand stroke required 7% more VO2 at low speed than forehand stroke (p < 0.05) while the additional cost of striking the ball lies between 3.5 and 3.0 mL kg-1 min-1. Finally, while striking the ball, the energy expanded during a shuttle displacement on half-width court is 14% higher than running on full-width court. Studies #2 and #3 focused on different modes of displacement observed in irregular sports. The objective of the second study was to measure and compare VO2, HR and [LA] responses to randomly performed multiple fractioned runs with directional changes (SR) and without directional changes (FR) to those of in-line running (IR) at speeds corresponding to 60, 70 and 80% of the subject’s maximal aerobic speed (MAS). All results show that IR’s VO2 was significantly lower than SR’s and FR’s (p<0.05). SR’s VO2 was greater than FR’s only at speeds corresponding to 80%MAS. On the other hand, HR was similar in SR and FR but significantly higher than IR’s (p<0.05). [LA] varied between 4.2 ± 0.8 and 6.6 ± 0.9 mmol L-1 without significant differences between the 3 displacement modes. Finally, the third study’s objective was to measure and compare VO2 , HR and [LA] responses during directional changes at different angles and at different submaximal running speeds corresponding to 60, 70 and 80% MAS. Subjects randomly performed 4 running protocols 1) a 20-m shuttle running course (180°) (SR), 2) an 8-shaped running course with 90-degree turns every 20 m (90R), 3) a Zigzag running course (ZZR) with multiple close directional changes (~ 5 m) at different angle values of 91.8°, 90° and 38.6°, 4) an In-line run (IR) for comparison purposes. Results show that IR’s was lower (p<0.001) than for 90R’s, SR’s and ZZR’s at all intensities. VO2 obtained at 60 and 70%MAS was 48.7 and 38.1% higher during ZZR when compared to IR while and depending on the intensity, during 90R and SR was between 15.5 and 19.6% higher than during IR. Also, ZZR’s VO2 was 26.1 and 19.5% higher than 90R’s, 26.1 and 15.5% higher than SR’s at 60 and 70%MAS. SR’s and 90R’s VO2 were similar. Changing direction at a 90° angle and at 180° angle seem similar when compared to continuous in-line running. [LA] levels were similar in all modalities. Overall, the studies presented in this thesis allow the quantification of the specific energetic demands of certain types of displacement modes in comparison with conventional forward running. Also, our results confirm that the energy cost varies and increase with the introduction of accelerations and decelerations with and without directional changes.

Increase brain lactate in hepatic encephalopathy: Cause or consequence?

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome which develops as a result of liver failure or disease. Increased concentrations of brain lactate (microdialysate, cerebrospinal fluid, tissue) are commonly measured in patients with HE induced by either acute or chronic liver failure. Whether an increase in brain lactate is a cause or a consequence of HE remains undetermined. A rise in cerebral lactate may occur due to (1) blood-borne lactate (hyperlactataemia) crossing the blood-brain barrier, (2) increased glycolysis due to energy failure or impairment and (3) increased lactate production/release or decreased lactate utilization/uptake. This review explores the different reasons for lactate accumulation in the brain during liver failure and describes the possible roles of lactate in the pathogenesis of HE.

Mild hypothermia prevents cerebral edema and CSF lactate accumulation in acute liver failure.

Evidence from both clinical and experimental studies demonstrates that mild hypothermia prevents encephalopathy and brain edema in acute liver failure (ALF). As part of a series of studies to elucidate the mechanism(s) involved in this protective effect, groups of rats with ALF resulting from hepatic devascularization were maintained at either 37°C (normothermic) or 35°C (hypothermic), and neurological status was monitored in relation to cerebrospinal fluid (CSF) concentrations of ammonia and lactate. CSF was removed via implanted cisterna magna catheters. Mild hypothermia resulted in a delay in onset of encephalopathy and prevention of brain edema; CSF concentrations of ammonia and lactate were concomitantly decreased. Blood ammonia concentrations, on the other hand, were not affected by hypothermia in ALF rats. These findings suggest that brain edema and encephalopathy in ALF are the consequence of ammonia-induced impairment of brain energy metabolism and open the way for magnetic resonance spectroscopic monitoring of cerebral function in ALF. Mild hypothermia could be beneficial in the prevention of severe encephalopathy and brain edema in patients with ALF awaiting liver transplantation.

Association of reduced extracellular brain ammonia, lactate, and intracranial pressure in pigs with acute liver failure.

We previously demonstrated in pigs with acute liver failure (ALF) that albumin dialysis using the molecular adsorbents recirculating system (MARS) attenuated a rise in intracranial pressure (ICP). This was independent of changes in arterial ammonia, cerebral blood flow and inflammation, allowing alternative hypotheses to be tested. The aims of the present study were to determine whether changes in cerebral extracellular ammonia, lactate, glutamine, glutamate, and energy metabolites were associated with the beneficial effects of MARS on ICP. Three randomized groups [sham, ALF (induced by portacaval anastomosis and hepatic artery ligation), and ALF+MARS] were studied over a 6-hour period with a 4-hour MARS treatment given beginning 2 hours after devascularization. Using cerebral microdialysis, the ALF-induced increase in extracellular brain ammonia, lactate, and glutamate was significantly attenuated in the ALF+MARS group as well as the increases in extracellular lactate/pyruvate and lactate/glucose ratios. The percent change in extracellular brain ammonia correlated with the percent change in ICP (r(2) = 0.511). Increases in brain lactate dehydrogenase activity and mitochondrial complex activity for complex IV were found in ALF compared with those in the sham, which was unaffected by MARS treatment. Brain oxygen consumption did not differ among the study groups. Conclusion: The observation that brain oxygen consumption and mitochondrial complex enzyme activity changed in parallel in both ALF- and MARS-treated animals indicates that the attenuation of increased extracellular brain ammonia (and extracellular brain glutamate) in the MARS-treated animals reduces energy demand and increases supply, resulting in attenuation of increased extracellular brain lactate. The mechanism of how MARS reduces extracellular brain ammonia requires further investigation.