title: Changes of pH and energy state in subacute human ischemia assessed by multinuclear magnetic resonance spectroscopy.
abstract: OBJECTIVE
  In vivo changes in tissue pH and energy metabolism are key to understanding stroke pathophysiology. Our goal was to study pH changes in subacute ischemic stroke and their relation to energy metabolism, which, unlike acidosis in acute stroke, are not yet well understood.
  
  
  METHODS
  We measured tissue pH and phospholipid as well as cell energy markers, including creatine, phosphocreatine, and N-acetyl-aspartate in subacute stroke with combined (1)H and (31)P magnetic resonance spectroscopy. We included 19 patients with first-ever ischemic stroke (mean time after stroke, 6 days). We then compared metabolite concentrations in the ischemic tissue to contralateral (healthy) tissue using multivariate ANOVA to assess significant differences in metabolite levels between both tissue compartments.
  
  
  RESULTS
  In subacute stroke, a tissue fraction with significantly increased tissue pH was observed as compared with healthy contralateral tissue (pH, 7.09 versus 7.03; P=0.002) concurrent with splitting of the pH signal with 1 peak being more alkalotic. Furthermore, only a moderate decrease of energy-rich metabolites (phosphocreatine reduced by 17%, ATP reduced by 19%) was present, whereas total creatine was reduced by 51%.
  
  
  CONCLUSIONS
  The finding of an alkalotic pH split in subacute ischemia is unprecedented. The pH split and only incomplete energy loss in subacute stroke suggest 2 differently viable cellular moieties, best explained by active compensatory mechanisms after acute cerebral ischemia.
authors.affiliation: From the Department of Neurology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany (J.P.Z., O.C.S) and Institute of Neuroradiology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany (E.H., U.P.).
authors.forename: Johann Philipp
authors.initials: JP
authors.lastname: Zöllner
authors.affiliation: From the Department of Neurology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany (J.P.Z., O.C.S) and Institute of Neuroradiology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany (E.H., U.P.).
authors.forename: Elke
authors.initials: E
authors.lastname: Hattingen
authors.affiliation: From the Department of Neurology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany (J.P.Z., O.C.S) and Institute of Neuroradiology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany (E.H., U.P.). o.singer@em.uni-frankfurt.de.
authors.forename: Oliver C
authors.initials: OC
authors.lastname: Singer
authors.affiliation: From the Department of Neurology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany (J.P.Z., O.C.S) and Institute of Neuroradiology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany (E.H., U.P.).
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pilatus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000175:diagnosis* / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods
keywords: energy metabolism; lactate; magnetic resonance spectroscopy; pH