title: Pressure overload-induced mild cardiac hypertrophy reduces left ventricular transmural differences in mitochondrial respiratory chain activity and increases oxidative stress.
abstract: OBJECTIVE
  Increased mechanical stress and contractility characterizes normal left ventricular (LV) subendocardium (Endo) but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi) and whether pressure overload-induced LV hypertrophy (LVH) might modulate transmural gradients through increased reactive oxygen species (ROS) production is unknown.
  
  
  METHODS
  LVH was induced by 6 weeks abdominal aortic banding and cardiac structure and function were determined with echocardiography and catheterization in sham-operated and LVH rats (n = 10 for each group). Mitochondrial respiration rates, coupling, content and ROS production were measured in LV Endo and Epi, using saponin-permeabilized fibers, Amplex Red fluorescence and citrate synthase activity.
  
  
  RESULTS
  In sham, a transmural respiratory gradient was observed with decreases in endo maximal oxidative capacity (-36.7%, P < 0.01) and complex IV activity (-57.4%, P < 0.05). Mitochondrial hydrogen peroxide (H(2)O(2)) production was similar in both LV layers. Aortic banding induced mild LVH (+31.7% LV mass), associated with normal LV fractional shortening and end diastolic pressure. LVH reduced maximal oxidative capacity (-23.6 and -33.3%), increased mitochondrial H(2)O(2) production (+86.9 and +73.1%), free radical leak (+27.2% and +36.3%) and citrate synthase activity (+27.2% and +36.3%) in Endo and Epi, respectively. Transmural mitochondrial respiratory chain complex IV activity was reduced in LVH (-57.4 vs. -12.2%; P = 0.02).
  
  
  CONCLUSIONS
  Endo mitochondrial respiratory chain complexes activities are reduced compared to LV Epi. Mild LVH impairs mitochondrial oxidative capacity, increases oxidative stress and reduces transmural complex IV activity. Further studies will be helpful to determine whether reduced LV transmural gradient in mitochondrial respiration might be a new marker of a transition from uncomplicated toward complicated LVH.
authors.affiliation: Service de Chirurgie Cardiovasculaire, Pôle d'activité médico-chirurgicale Cardiovasculaire, Hôpitaux Universitaires, CHRU Strasbourg Strasbourg, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Kindo
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gerelli
authors.forename: Jamal
authors.initials: J
authors.lastname: Bouitbir
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Charles
authors.forename: Joffrey
authors.initials: J
authors.lastname: Zoll
authors.forename: Tam
authors.initials: T
authors.lastname: Hoang Minh
authors.forename: Laurent
authors.initials: L
authors.lastname: Monassier
authors.forename: Fabrice
authors.initials: F
authors.lastname: Favret
authors.forename: François
authors.initials: F
authors.lastname: Piquard
authors.forename: Bernard
authors.initials: B
authors.lastname: Geny