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Introduction Chronic hypoxia (CH) occurs under certain physiological (high altitude) or pathological conditions (chronic pulmonary diseases). Adaptation to CH has been extensively studied in animals and humans (Leverve 1998). CH [...], Chronic hypoxia alters mitochondrial energy metabolism. In the heart, oxidative capacity of both ventricles is decreased after 3 weeks of chronic hypoxia. The aim of this study was to evaluate the reversal of these metabolic changes upon normoxia recovery. Rats were exposed to a hypobaric environment for 3 weeks and then subjected to a normoxic environment for 3 weeks (normoxia-recovery group) and compared with rats maintained in a normoxic environment (control group). Mitochondrial energy metabolism was differentially examined in both left and right ventricles. Oxidative capacity (oxygen consumption and ATP synthesis) was measured in saponin-skinned fibers. Activities of mitochondrial respiratory chain complexes and antioxidant enzymes were measured on ventricle homogenates. Morphometric analysis of mitochondria was performed on electron micrographs. In normoxia-recovery rats, oxidative capacities of right ventricles were decreased in the presence of glutamate or palmitoyl carnitine as substrates. In contrast, oxidation of palmitoyl carnitine was maintained in the left ventricle. Enzyme activities of complexes III and IV were significantly decreased in both ventricles. These functional alterations were associated with a decrease in numerical density and an increase in size of mitochondria. Finally, in the normoxia-recovery group, the antioxidant enzyme activities (catalase and glutathione peroxidase) increased. In conclusion, alterations of mitochondrial energy metabolism induced by chronic hypoxia are not totally reversible. Reactive oxygen species could be involved and should be investigated under such conditions, since they may represent a therapeutic target. Key words: chronic hypoxia, reoxygenation, rat heart, mitochondria, energy metabolism, oxidative phosphorylation, antioxidants. L'hypoxie chronique modifie le metabolisme energetique des mitochondries. Dans le coeur, la capacite oxydative des 2 ventricules diminue apres 3 semaines d'hypoxie chronique. La presente etude a eu pour but d'evaluer la reversibilite des modifications metaboliques lors du retour en normoxie. On a expose des rats a un environnement hypobare pendant 3 semaines, puis a un environnement normoxique pendant 3 semaines (groupe retour en normoxie), et on les a ensuite compares avec des rats maintenus dans un environnement normoxique (groupe teemoin). On a examine; le metabolisme energetique des mitochondries dans les ventricules gauche et droit. On a mesure la capacite oxydative (consommation d'oxygene et synthese d'ATP) dans des fibres pelees a l'aide de saponine. On a mesure les activiteis des complexes de la chaine respiratoire mitochondriale et d'enzymes antioxydantes sur des homogenats de ventricules. On a effectue; une analyse morphomeetrique des mitochondries en microscopie eelectronique. Chez les rats du groupe retour en normoxie, les capacites oxydatives du ventricule droit ont diminue lorsque le glutamate ou la palmitoyl carnitine ont ete utilises comme substrats. A l'oppose, l'oxydation de la palmitoyl carnitine a ete maintenue dans le ventricule gauche. Les activites enzymatiques des complexes III et IV ont diminue de maniere significative dans les 2 ventricules. Ces modifications fonctionnelles ont ete associees a une diminution de la densite numerique et a une augmentation de la taille des mitochondries. Enfin, chez le groupe retour en normoxie, les activites des enzymes antioxydantes (catalase et glutathion peroxydase) ont augmente. Ainsi, les modifications du metabolisme energetique des mitochondries induites par l'hypoxie chronique ne sont pas totalement reversibles. Les ROS pourraient etre en cause et devraient etre examines dans ces conditions puisqu'elles pourraient representer une cible therapeutique. Mots-cles: hypoxie chronique, reoxygenation, coeur de rat, mitochondrie, metabolisme energetique, phosphorylation oxydative, antioxydants.

Introduction Different forms of dietary restrictions without malnutrition, such as reduction in caloric intake and alternate-day fasting, result in marked adaptations in the rat myocardium. These adaptations include induction of [...], The goal of the present study was to assess the effects of a restricted feeding schedule (RFS) on postischemic contractile recovery in relation to triacylglycerol (TAG), glycogen, and ATP content. Glucose-6-phosphate dehydrogenase (G6PDH) activity, reduced/oxidized glutathione ratio (GSH/GSSG), and thiobarbituric acid reactive substances (TBARS) levels were also determined. Isolated rat hearts entrained to daily RFS (2 h food access starting at 1200) or fed ad libitum (FED) for 3 weeks were Langendorff-perfused (25 min ischemia, 30 min reperfusion) with Krebs-Ringer bicarbonate solution (10 mmol/L glucose). RFS improved the recovery of contractility and reduced creatine kinase (CK) release upon reperfusion. Further, at the end of reperfusion, RFS hearts exhibited increased G6PDH activity and repletion of tissue glycogen, TAG, and ATP that was not observed in the FED hearts. GSH/GSSG at the end of reperfusion fell to the same value in both nutritional states, and TBARS levels were higher in the RFS hearts. In conclusion, RFS improved postischemic functional recovery, which was accompanied by a reduction in CK release and a striking energy recovery. Although enhanced G6PDH activity was displayed, RFS was unable to reduce lipid peroxidation, supporting a clear dissociation between protection against mechanical dysfunction and CK release on the one hand and oxidative damage on the other. Key words: restricted feeding schedule, ischemia-reperfusion, heart, triacylglycerol, glycogen, ATP. La presente etude a eu pour but d'evaluer les effets d'un programme d'alimentation rationneee (PAR) sur le retablissement de la force contractile postischemique en relation avec la teneur en triacylglycerol (TAG), en glycogene et en ATP. Elle a aussi determine l'activite de la glucose-6-phosphate deeshydrogenase (G6PDH), le rapport glutathion reduit/ oxyde (GSH/GSSG) et les taux de substances reactives a l'acide thiobarbiturique (TBARS). Les coeurs isolees de rats entrainesa un PAR quotidien (accesa la nourriture pendant 2 h a partir de midi) ou alimentees ad libitum (AAL) pendant 3 semaines ont ete perfuses selon la methode de Langendorff (ischeemie de 25 min, reperfusion de 30 min) avec une solution Krebs-Ringer bicarbonateee (10 mmol/L de glucose). Le PAR a ameliore le retablissement de la force contractile et reduit la liberation de creatine kinase (CK) lors de la reperfusion. A la fin de la reperfusion, les coeurs des rats soumis au PAR ont montre une augmentation de l'activite; de la G6DPH et une recharge en glycogene, TAG et ATP qui n'ont pas ete observeees dans les coeurs des rats AAL. De plus, le rapport GSH/GSSG a diminuee a une valeur identique dans les deux etats nutritionnels, et les taux de TBARS ont ete plus eelevees dans les coeurs PAR. En conclusion, le PAR a ameliore le retablissement fonctionnel postichemique, qui a ete accompagne d'une reduction de la liberation de CK et d'un retablissement significatif du metabolisme energetique. Malgre une augmentation de l'activite de la G6DPH, le PAR n'a pu diminue la peroxydation lipidique, ce qui deemontre une dissociation nette entre une protection contre la dysfonction mecanique et la liberation de CK, d'une part, et le dommage oxydatif, d'autre part. Mots-cles: programme d'alimentation restreinte, ischeemie-reperfusion, coeur, triacylglycerol, glycogene, ATP. [Traduit par la Redaction]

doi:10.1152/physreve.00002.2005.--The heart is a rhythmic electromechanical pump, the functioning of which depends on action potential generation and propagation, followed by relaxation and a period of refractoriness until the next impulse [...]

We analyzed the thermal limits of heart function for congeneric species of the marine snail Tegula that have different patterns of vertical zonation. T. funebralis is found in the low to mid-intertidal zone, and T. brunnea and T. montereyi live in the low-intertidal or subtidally. As indices of thermal limits of heart function, we used the temperature at which heart rate initially decreased rapidly during heating (the Arrhenius break temperature, or ABT) and the temperature at which heart ceased to beat with either heating or cooling (the flatline temperature, or FL[T.sub.hot] or FL[T.sub.cold], respectively). These three indices provide an estimate of the thermal range within which Tegula heart function is maintained. For field-acclimatized specimens, the thermal range of the high-intertidal T. funebralis was greater than those of its two lower-occurring congeners (higher ABT, higher FL[T.sub.hot], lower FL[T.sub.cold]). We also demonstrated the effects of constant thermal acclimation on the heart rate response to heat stress. Acclimation to 14°C and 22°C resulted in increases in ABT and FL[T.sub.hot], with the largest changes in T. brunnea and T. montereyi. Although T. funebralis is more heat tolerant and eurythermal than its two lower-occurring congeners, it can encounter field body temperatures that exceed ABT, indicating that T. funebralis faces a larger threat from heat stress, in situ. These findings are consistent with recent studies on other taxa of marine invertebrates that have shown, somewhat paradoxically, that warm-adapted, eurythermal intertidal species may be more impacted by global warming than congeneric subtidal species that are less heat tolerant., Introduction Physiological adaptations to temperature in ectothermic species are pervasive and have long been regarded as important in establishing biogeographic patterning along latitudinal thermal gradients (Bullock, 1955). Studies of many [...]