title: Endotoxemia causes a paradoxical intracellular pH recovery in exercising rat skeletal muscle.
abstract: In resting skeletal muscle, endotoxemia causes disturbances in energy metabolism that could potentially disturb intracellular pH (pH(i)) during muscular activity. We tested this hypothesis using in situ (31)P-magnetic resonance spectroscopy in contracting rat gastrocnemius muscle. Endotoxemia was induced by injecting rats intraperitoneally at t(0) and t(0) + 24 h with Klebsiella pneumoniae endotoxin (lipopolysaccharides at 3 mg/kg) or saline vehicle. Muscle function was investigated strictly noninvasively at t(0) + 48 h through a transcutaneous electrical stimulation protocol consisting of 5.7 minutes of repeated isometric contraction at 3.3 HZ, and force production was measured with an ergometer. At rest, endotoxin treatment did not affect pH(i) and adenosine triphosphate concentration, but significantly reduced phosphocreatine and glycogen contents. Endotoxemia produced both a reduction of isometric force production and a marked linear recovery (0.08 +/- 0.01 pH unit/min) of pH(i) during the second part of the stimulation period. This recovery was not due to any phenomenon of fiber inactivation linked to development of muscle fatigue, and was not associated with any change in intracellular proton buffering, net proton efflux from the cell, or proton turnovers through creatine kinase reaction and oxidative phosphorylation. This paradoxical pH(i) recovery in exercising rat skeletal muscle under endotoxemia is likely due to slowing of glycolytic flux following the reduction in intramuscular glycogen content. These findings may be useful in the follow-up of septic patients and in the assessment of therapies.
authors.affiliation: Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR CNRS 6612, Faculté de Médecine de Marseille, 27 Boulevard Jean Moulin, 13005, Marseille, France. benoit.giannesini@medecine.univ-mrs.fr
authors.forename: Benoît
authors.initials: B
authors.lastname: Giannesini
authors.forename: Marguerite
authors.initials: M
authors.lastname: Izquierdo
authors.forename: Christiane
authors.initials: C
authors.lastname: Dalmasso
authors.forename: Yann
authors.initials: Y
authors.lastname: Le  Fur
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Cozzone
authors.forename: Marc
authors.initials: M
authors.lastname: Verleye
authors.forename: Marie-Emmanuelle
authors.initials: ME
authors.lastname: Le  Guern
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Gillardin
authors.forename: David
authors.initials: D
authors.lastname: Bendahan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D019446:Endotoxemia / Q000378:metabolism* / Q000503:physiopathology / Q000534:rehabilitation*; D004734:Energy Metabolism; D006003:Glycogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology; D010805:Physical Conditioning, Animal / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000255:Adenosine Triphosphate; D006003:Glycogen