title: Lactate kinetics and mitochondrial respiration in skeletal muscle of healthy humans under influence of adrenaline.
abstract: Plasma lactate is widely used as a biomarker in critical illness. The aims of the present study were to elucidate the usefulness of a three-compartment model for muscle lactate kinetics in humans and to characterize the response to an exogenous adrenaline challenge. Repeated blood samples from artery and femoral vein together with blood flow measurements and muscle biopsies were obtained from healthy male volunteers (n=8) at baseline and during an adrenaline infusion. Concentrations of lactate and enrichment of [13C]lactate were measured and kinetics calculated. Mitochondrial activity, glycogen concentration, oxygen uptake and CO2 release were assessed. The adrenaline challenge increased plasma lactate 4-fold as a result of a greater increase in the rate of appearance (R(a)) than the increase in the rate of disappearance (R(d)). Leg muscle net release of lactate increased 3.5-fold, whereas intramuscular production had a high variation but did not change. Mitochondrial state 3 respiration increased by 30%. Glycogen concentration, oxygen uptake and CO2 production remained unchanged. In conclusion a three-compartment model gives additional information to the two-compartment model but, due to its larger variation and invasive muscle biopsy, it is less likely to become a regularly used tool in clinical research. Hyperlactataemia in response to adrenergic stimuli was driven by an elevated lactate release from skeletal muscle most probably due to a redirection of a high intramuscular turnover rather than an increased production.
authors.affiliation: *Clintec, Department of Anesthesiology and Intensive Care, Karolinska Institutet and Karolinska University Hospital, 141 86 Huddinge, Sweden.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Grip
authors.affiliation: *Clintec, Department of Anesthesiology and Intensive Care, Karolinska Institutet and Karolinska University Hospital, 141 86 Huddinge, Sweden.
authors.forename: Towe
authors.initials: T
authors.lastname: Jakobsson
authors.affiliation: *Clintec, Department of Anesthesiology and Intensive Care, Karolinska Institutet and Karolinska University Hospital, 141 86 Huddinge, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Hebert
authors.affiliation: *Clintec, Department of Anesthesiology and Intensive Care, Karolinska Institutet and Karolinska University Hospital, 141 86 Huddinge, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Klaude
authors.affiliation: *Clintec, Department of Anesthesiology and Intensive Care, Karolinska Institutet and Karolinska University Hospital, 141 86 Huddinge, Sweden.
authors.forename: Gustaf
authors.initials: G
authors.lastname: Sandström
authors.affiliation: *Clintec, Department of Anesthesiology and Intensive Care, Karolinska Institutet and Karolinska University Hospital, 141 86 Huddinge, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Wernerman
authors.affiliation: *Clintec, Department of Anesthesiology and Intensive Care, Karolinska Institutet and Karolinska University Hospital, 141 86 Huddinge, Sweden.
authors.forename: Olav
authors.initials: O
authors.lastname: Rooyackers
mesh_terms: D000322:Adrenergic Agonists / Q000008:administration & dosage*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D019069:Cell Respiration / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage*; D006003:Glycogen / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D007700:Kinetics; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D010101:Oxygen Consumption / Q000187:drug effects; D010865:Pilot Projects; D052097:Quadriceps Muscle / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000322:Adrenergic Agonists; D015415:Biomarkers; D019344:Lactic Acid; D006003:Glycogen; D004837:Epinephrine