Increased mitochondrial energy efficiency in skeletal muscle after long-term fasting: its relevance to animal performance.

In the final stage of fasting, skeletal muscle mass and protein content drastically decrease when the maintenance of efficient locomotor activity becomes crucial for animals to reactivate feeding behaviour and survive a very long period of starvation. As mitochondrial metabolism represents the main physiological link between the endogenous energy store and animal performance, the aim of this study was to determine how a very long, natural period of fasting affected skeletal muscle mitochondrial bioenergetics in king penguin (Aptenodytes patagonicus) chicks. Rates of mitochondrial oxidative phosphorylation were measured in pectoralis permeabilized fibres and isolated mitochondria. Mitochondrial ATP synthesis efficiency and the activities of respiratory chain complexes were measured in mitochondria isolated from pectoralis muscle. Results from long-term (4-5 months) naturally fasted chicks were compared with those from short-term (10 day) fasted birds. The respiratory activities of muscle fibres and isolated mitochondria were reduced by 60% and 45%, respectively, on average in long-term fasted chicks compared with short-term fasted birds. Oxidative capacity and mitochondrial content of pectoralis muscle were lowered by long-term fasting. Bioenergetic analysis of pectoralis muscle also revealed that mitochondria were, on average, 25% more energy efficient in the final stage of fasting (4-5 months) than after 10 days of fasting (short-term fasted birds). These results suggest that the strong reduction in respiratory capacity of pectoralis muscle was partly alleviated by increased mitochondrial ATP synthesis efficiency. Such oxidative phosphorylation optimization can impact animal performance, e.g. the metabolic cost of locomotion or the foraging efficiency.

Electrophysiological, haemodynamic, and mitochondrial alterations induced by levobupivacaine during myocardial ischemia in a pig model: protection by lipid emulsions?

Accidental intravascular or high-dose injection of local anesthetics (LA) can result in serious, potentially life-threatening complications. Indeed, adequate supportive measures and the administration of lipid emulsions are required in such complications. The study's objectives were threefold: (i) evaluate the myocardial toxicity of levobupivacaine when administered intravenously; (ii) investigate levobupivacaine toxicity on cardiomyocytes mitochondrial functions and cellular structure; (iii) assess the protective effects of a lipid emulsion in the presence or absence of myocardial ischemia. Domestic pigs randomized into two groups of 24 animals each, with either preserved coronary circulation or experimental myocardial ischemia. Six animals from each group received either: (i) single IV injection of saline, (ii) lipid emulsion (Intralipid(®) ), (iii) levobupivacaine, (iv) combination levobupivacaine-Intralipid(®) . Serially measured endpoints included: heart rate, duration of the monophasic action potentials (dMAP), mean arterial pressure, and peak of the time derivative of left ventricular pressure (LV dP/dtmax ). In addition, the following cardiomyocytes mitochondrial functions were measured: reactive oxygen species (ROS) production, oxidative phosphorylation, and calcium retention capacity (CRC) as well as the consequences of ROS production on lipids, proteins, and DNA. IV injection of levobupivacaine induced sinus bradycardia and reduced dMAP and LV dP/dtmax . At the mitochondrial level, oxygen consumption and CRC were decreased. In contrast, ROS production was increased leading to enhanced lipid peroxidation and structural alterations of proteins and DNA. Myocardial ischemia was associated with global worsening of all changes. Intralipid(®) quickly improved haemodynamics. However, beneficial effects of Intralipid(®) were less clear after myocardial ischemia.