title: Myocardial energy metabolism and morphology in a canine model of sepsis.
abstract: The mechanism responsible for sepsis-induced myocardial depression is not known. To determine if sepsis-induced myocardial depression is caused by inadequate free energy available for work, we studied myocardial energy metabolism in a canine model of sepsis. Escherichia coli-infected (n = 18) or sterile (n = 16) fibrin clots were implanted intraperitoneally into beagles. Myocardial function and structure was assessed using radionuclide ventriculograms, echocardiograms, and light and electron microscopy. The adequacy of energy metabolism was evaluated by comparing catecholamine-induced work increases [myocardial O2 consumption (MVO2) and rate pressure product (RPP)] with a simultaneously obtained estimate of intracellular free energy [phosphocreatine-to-adenosine triphosphate ratio (PCr:ATP)] determined by 31P-magnetic resonance spectroscopy. When compared with control animals, septic animals had a decrease in left ventricular ejection fraction (EF, P < 0.0001) on day 1 and fractional shortening (FS, P < 0.0003) on day 2 after clot implantation. On day 2, neither septic nor control animals had statistically significant decreases in PCr:ATP, despite catecholamine-induced increases in MVO2 and RPP (mean maximal increases in septic animals 135 +/- 31 and 51 +/- 10%, respectively). Light and electron microscopic findings showed that hearts of septic animals, compared with control animals, had a greater degree of morphological abnormalities. Thus, in a canine model of sepsis with alterations in myocyte ultrastructure and documented myocardial depression (decreased EF and FS), intracellular free energy levels (PCr:ATP) were maintained despite catecholamine-induced increases in myocardial work (increased MVO2 and RPP), suggesting high-energy synthetic capabilities are not limiting cardiac function.
authors.affiliation: Critical Care Medicine Department, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: M A
authors.initials: MA
authors.lastname: Solomon
authors.forename: R
authors.initials: R
authors.lastname: Correa
authors.forename: H R
authors.initials: HR
authors.lastname: Alexander
authors.forename: L A
authors.initials: LA
authors.lastname: Koev
authors.forename: J P
authors.initials: JP
authors.lastname: Cobb
authors.forename: D K
authors.initials: DK
authors.lastname: Kim
authors.forename: W C
authors.initials: WC
authors.lastname: Roberts
authors.forename: Z M
authors.initials: ZM
authors.lastname: Quezado
authors.forename: T D
authors.initials: TD
authors.lastname: Scholz
authors.forename: R E
authors.initials: RE
authors.lastname: Cunnion
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016470:Bacteremia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D004730:Endothelium, Vascular / Q000473:pathology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D008929:Mitochondria, Heart / Q000473:pathology; D008933:Mitochondrial Swelling; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D009210:Myofibrils / Q000473:pathology / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D010725:Phosphocreatine / Q000378:metabolism; D012016:Reference Values; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D010725:Phosphocreatine; D010656:Phenylephrine; D000255:Adenosine Triphosphate; D004837:Epinephrine