title: Real-time assessment of ¹³C metabolism reveals an early lactate increase in the brain of rats with acute liver failure.
abstract: Intracranial hypertension is a severe complication of acute liver failure (ALF) secondary to brain edema. The pathogenesis of cerebral edema in ALF is not clear, but seems to be related to energy metabolism in which lactate may have an important role. The aim of this study was to follow the synthesis of brain lactate using a novel in vivo metabolic technology in a rat model of ALF. Time-resolved (13) C MRS of hyperpolarized (13) C1 -pyruvate was used to quantitatively follow the in vivo conversion of pyruvate to its substrates in a model of devascularized ALF in rats. Rats with ALF showed a significant increase in the lactate to pyruvate ratio from 36% to 69% during the progression of liver disease relative to rats with portocaval anastomosis. Rats with ALF also showed a significant increase in the alanine to pyruvate ratio from 72% to 95%. These increases were detectable at very early stages (6 h) when animals had no evident disease signs in their behavior (without loss of righting or corneal reflexes). This study shows the dynamic consequences of cerebral in vivo (13) C metabolism at real time in rats with ALF. The early detection of the de novo synthesis of lactate suggests that brain lactate is involved in the physiopathology of ALF. Hyperpolarization is a potential non-invasive technique to follow the in vivo metabolism, and both the development and optimization of (13) C-labeled substrates can clarify the mechanism involved in ALF.
authors.affiliation: Liver Unit, Hospital Vall Hebron, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Chavarria
authors.forename: Jordi
authors.initials: J
authors.lastname: Romero-Giménez
authors.forename: Eva
authors.initials: E
authors.lastname: Monteagudo
authors.forename: Silvia
authors.initials: S
authors.lastname: Lope-Piedrafita
authors.forename: Juan
authors.initials: J
authors.lastname: Cordoba
mesh_terms: D000409:Alanine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism*; D002247:Carbon Isotopes; D003199:Computer Systems; D018450:Disease Progression; D019344:Lactic Acid / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000378:metabolism*; D008297:Male; D019289:Pyruvic Acid / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D002247:Carbon Isotopes; D019344:Lactic Acid; D002244:Carbon; D019289:Pyruvic Acid; D000409:Alanine
keywords: acute liver failure; dynamic nuclear polarization; hyperpolarization; in vivo spectroscopy; lactate