Philippe Sébert

Effects of mild induced hypothermia during experimental sepsis.

Objectives:The potential advantages of lowering core temperature during sepsis are to lower energy requirement and to activate various cell-protecting pathways. We experimentally investigated whether postconditioning temperature modifications influence survival duration during experimental sepsis. Design:A prospective, randomized, experimental animal study. Setting:University laboratory. Subjects:Eighteen male Sprague-Dawley rats (median 326 g, range 310–347 g). Interventions:After anesthesia, experimental sepsis was induced by cecal ligation and perforation. The animals were subsequently assigned a core temperature range: normothermia (37°C), hyperthermia (42°C), and mild hypothermia (32°C). Anesthesia and analgesia were continuously maintained until death. Measurements and Main Results:Plasma lactate and pyruvate concentrations were measured at sepsis induction (H0), 4 hrs later (H4), and/or at the time of death. A significant increase in lactate concentration was observed at the time of death in the 42°C group (p = .04). Lactate-to-pyruvate ratio increased in the 32°C (at H4) and 42°C (at the time of death) groups (p = .04). A linear correlation between a longer survival duration and a lower assigned core temperature was observed (from 61 ± 10 mins at 42°C to 289 ± 17 mins at 37°C and to 533 ± 69 mins at 32°C; R2 = .959, p < .0001). Conclusions:The current results demonstrate that postconditioning hypothermia was associated with increased survival duration during experimental sepsis. Whether the observed benefits on survival duration are due to potential impacts on energy metabolism or to an anti-inflammatory effect of hypothermia requires further investigation.

Laboratory system enabling long-term exposure (⩾ 30 d) to hydrostatic pressure (⩽ 101 atm) of fishes or other animals breathing water

A high-pressure water-circulation system is described which enables fish (or other animals breathing water) to be maintained at pressures up to 101 atm for at least one month. A typical experiment, measuring the oxygen consumption of the eelAnguilla anguilla over a period of 31 d, revealed a metabolic acclimation to pressure in this fish. This system has numerous advantages; e.g. it is possible to reproduce in situ environmental conditions at depth, thus enabling the study of the problems of pressure adaptation, and also to simulate vertical migrations of animals, allowing the study of associated physiological phenomenon.

High hydrostatic pressure improves the swimming efficiency of European migrating silver eel

To reproduce, European eels must undergo a long migration without feeding. During this migration they have to cope with many environmental factor changes, one of them being hydrostatic pressure. We focus on the effects of hydrostatic pressure on swimming energetics: does the pressure exposure modify swimming efficiency? By using a specially designed Blazka type swimming tunnel able to work under pressure, we have measured oxygen consumption of migrating male silver eels at different swimming speeds (from 0.2 to 1.0 BL/s) first at atmospheric pressure then at 101 ATA hydrostatic pressure. The results show that pressure increases the energetic swimming efficiency by decreasing oxygen consumption for a given swimming speed. Such a pressure effect could represent a remarkable adaptation enabling eels to spare their energy stores and swim for a long time.

Hydrostatic pressure induces a state resembling histotoxic hypoxia in Anguilla anguilla

Abstract 1. 1. Energy metabolism (substrates, enzyme activities) was studied in white muscle and liver of yellow freshwater eels ( Anguilla anguilla L.) exposed for 3 hr to 100 atm hydrostatic pressure in normoxic conditions and at constant water temperature. 2. 2. In the two tissues explored, a decrease occurred in glycogen content (the anaerobic substrate) and an accumulation of total fatty acids (exclusive aerobic substrate). Concomitant changes in substrate contents, decreased of cytochrome c oxidase activity and increased lactate dehydrogenase activity were observed. 3. 3. When complemented with observations (ATP, oxygen consumption) from previous studies, results were in agreement with an alteration of aerobic energy production and an activation of the anaerobic pathway. In fish, hydrostatic pressure appeared to induce a state resembling histotoxic hypoxia.

Effects of hydrostatic pressure per se (101 ATA) on energetic processes in fish.

Nucleotides concentrations (ATP, ADP, AMP) have been measured in brain and muscle of eels exposed to 101 ATA of hydrostatic pressure (HP) for 3 hr. Survival times (ST) and oxygen arterial content (CaO2) have been measured in trouts exposed to HP = 101 ATA. The results show that at HP = 101 ATA, AMP increases (P less than 0.05) and ATP decreases (-12%; NS) in muscle but are not modified in brain; ST values are similar in normoxic and hyperoxic conditions, and CaO2 are similar at 1 ATA and 101 ATA of HP. It is concluded that HP tends to decrease aerobic production of energy. This phenomenon is not due to a failure in O2 transport from ambient medium to the cell but to a possible perturbation of the aerobic cellular processes leading to energy production (Krebs cycle and/or respiratory chain coupled to oxidative phosphorylation.

Effects of Hydrostatic Pressure on Energy Metabolism and Osmoregulation in Crab and Fish

This review will focus on the effects of hydrostatic pressure on the oxidative metabolism and on the energy production of the eel Anguilla anguilla, in comparison with the results of investigations conducted on the other powerful euryhaline species, the chinese crab Eriocheir sinensis. Anguilla and Eriocheir were chosen as being both aquatic ectotherms with comparable life modes, the eel being however “preadapted” to high pressure while the crab normally never encounters high levels of pressure during its life cycle. Comparison between both species should lead to better knowledge of the biological effects of hydrostatic pressure per se. Experimental evidence suggests that the oxygen consumption ṀO2 decrease observed in both animal species during exposure to 101 ATA hydrostatic pressure and which follows a transient increase, likely results from a decrease in O2 use at the cell level. That idea of an alteration of aerobic metabolism during the first hours under pressure is substantiated by a set of experiments on the eel. However, results indicate that, after some days under pressure, the shallow water fish is quite able to acclimate perfectly to high pressure. The hypothesis that pressure induces a state resembling histotoxic hypoxia during the first hours of exposure is put forward and discussed. The second part of the review focuses on some results showing that osmoregulation is also concerned with hydrostatic pressure. Results obtained on the freshwater eel clearly establish the occurrence of a Na+ balance impairment at the tissue level induced by a long-term (30 days) exposure to pressure. It is interesting to point out that this impairment occurs at the same time when a new state of energetic metabolism results from adjustments of intertissue coupling of anaerobic and aerobic metabolisms induced by pressure. It is shown that the physiological processes involved in the control of the hydromineral balance in the chinese crab (which never experiences high-pressure exposure in the course of its life cycle) are outstandingly resistant to pressure by comparison with other crustaceans like the crayfish and the shore crab. Disturbances in hydromineral balance and energetic metabolism in the chinese crab are rapidly resorbed and adjusted to a new state of activity.

High hydrostatic pressure (101 ATA) changes the metabolic design of yellow freshwater eel muscle

The glycolytic pathway has been studied in the white muscle of yellow freshwater eel (Anguilla anguilla L.) exposed to high hydrostatic pressure (101 ATA) for 1 month. Using appropriate substrates and auxiliary enzymes to drive the flux towards glycerol phosphate, fluxes of glucose (JA) then of glucose 6-phosphate (JB) have been measured. The maximum acceleration during the transition from JA to JB was measured as the response time, tm; the metabolic reprise, which gives information about the rapidity of a given metabolic change, was calculated as r (JB:JA):tm, i.e the ratio of the fluxes over the response time. An estimation in vivo has been performed for each parameter. Acclimatization to high pressure induces a significant increase in the fluxes (PB0.05), but the ratio JB:JA remains constant. As the metabolic response time tm decreases, there is a significant increase in the metabolic reprise r (60%, PB0.01) which means that muscle from acclimatized fish has the capacity to increase the glycolytic flux 1.6-times more than control fish muscle. These modifications in the metabolic design in pressure acclimatized fish are discussed and the hypothesis is raised that pressure may optimize energy production to prepare eel physiology to the new environment encountered during migration from freshwater to seawater and thus to a new type of energy demand.

Carotid chemoreceptor function in ventilatory and circulatory O2 convection of exercising dogs at low and high altitude

Awake dogs were studied before (control) and after chronic bilateral carotid denervation (denervated) at rest and running for 3 min on a treadmill at 8 km . h-1 and at various grades, in an altitude chamber operated either at 140 m or at 4000 m for 3 h. Steady-state pulmonary ventilation (Vg) and breathing pattern (VT, fR), oxygen consumption (MO2), O2 concentrations (C) and pressures (P) in the arterial (a) and mixed venous blood (v), hematocrit (Ht) and acid-base status in arterial blood, and heart frequency (fH) were measured. From these data cardiac output (Vb) and stroke volume (Vs), ventilatory and circulatory requirements (Vg/Mo2, Vb/MO2), extraction of O2 from inspired gas (EairO2) and blood (EbO2), and capacitance coefficient of blood for oxygen (beta bO2) were calculated. Ventilatory responses to transient O2-inhalation were also studied and the aortic (AP) and pulmonary (PP) blood pressures measured in resting conditions. 1. After chronic carotid denervation the hypoxic chemoreflex drive of ventilation was reduced by about half, maximal MO2 remained unaffected at 140 m, but at 4000 m decreased 50% compared to 30% in controls. 2. In all experimental conditions, Vg/MO2, PaO2 and CaO2 were less in denervated animals than in controls, and EairO2, PaCO2 and H+ ion concentration were higher. 3. At 140 m, circulatory O2 convective transport was identical in the two groups of dogs. At 4000 m, beta bO2 increased similarly in both groups, but Vb and Vb/MO2 were higher in denervated dogs than in controls, in relation with reduced CaO2-CVO2 difference which contributed to restore PVO2 towards higher values. 4. At 140 m, mean resting AP and PP were similar in both groups of dogs. At 4000 m, AP increased not significantly in controls, and decreased in denervated animals; PP increased in controls, but not in denervated dogs. It is concluded that integrity of the arterial chemoreceptor drive is essential in determining the eupneic level of ventilation and normal acid-base status of the blood in both resting and exercising dogs, at low and at high altitude, and in reducing the O2 circulatory requirement at high altitude. At 4000 m, the lack of carotid chemosensitivity is accompanied by severe hypoxemia, in association with hypercapnia and acidosis, and by increased cardiac blood flow, most presumably due to decreased peripheral resistance and increased venous return; despite these compensatory changes in circulatory O2 convective transport, denervated animals reach a maximum O2 uptake at lower work load than controls.

Catecholamine content (as measured by the HPLC method) in brain and blood plasma of the eel: effects of 101 ata hydrostatic pressure☆

The catecholamine content (noradrenaline, NA; adrenaline, A; dopamine, DA, and its metabolite, DOPAC) was measured, by the HPLC method, in brain and blood plasma of eels studied at atmospheric pressure (1 ATA) or at 101 ATA of hydrostatic pressure (HP). In the brain, HP induces a slight but significant increase (P less than 0.05) in A and DA contents but NA and DOPAC levels are not modified at 101 ATA when compared to 1 ATA. In the plasma, only A and NA are detected, adrenaline being the predominant amine. In eels exposed to 101 ATA HP, A and NA are strongly increased (+100%; P less than 0.01). The significance of the catecholamine increase in brain and plasma of the eels under HP is discussed.

Effect of exercise training on respiration and reactive oxygen species metabolism in eel red muscle

This paper deals with the effects of exercise training on oxygen consumption (MO(2)) and ROS metabolism in the red muscle of trained and untrained female silver eels. Their critical swimming speed (U(crit)) was determined before and after a 4-day training (10h of swimming at 70% of U(crit) and 14 h at 50%, every day). The U(crit) of trained eels increased significantly (by about 7%). The in vitro MO(2) and ROS production by the red fibres were higher (not significant) in trained than in untrained eels, but the ROS production/MO(2) ratio was alike in both groups. The antioxidant-enzyme activities and lipoperoxidation index in trained eels were both lower than those of the untrained ones. These biochemical changes related to the increase in U(crit) suggest that such a training session could maintained or even increased aerobic power of the red muscle without deleterious impact by ROS. These regulations could play a role in the eels swimming performance efficiency.