title: Left Ventricular Transmural Gradient in Mitochondrial Respiration Is Associated with Increased Sub-Endocardium Nitric Oxide and Reactive Oxygen Species Productions.
abstract: OBJECTIVE
  Left ventricle (LV) transmural gradient in mitochondrial respiration has been recently reported. However, to date, the physiological mechanisms involved in the lower endocardium mitochondrial respiration chain capacity still remain to be determined. Since, nitric oxide (NO) synthase expression in the heart has spatial heterogeneity and might impair mitochondrial function, we investigated a potential association between LV transmural NO and mitochondrial function gradient.
  
  
  METHODS
  Maximal oxidative capacity (VMax) and relative contributions of the respiratory chain complexes II, III, IV (VSucc) and IV (VTMPD), mitochondrial content (citrate synthase activity), coupling, NO (electron paramagnetic resonance), and reactive oxygen species (ROS) production (H2O2 and dihydroethidium (DHE) staining) were determined in rat sub-endocardium (Endo) and sub-epicardium (Epi). Further, the effect of a direct NO donor (MAHMA NONOate) on maximal mitochondrial respiratory rates (Vmax) was determined.
  
  
  RESULTS
  Mitochondrial respiratory chain activities were reduced in the Endo compared with the Epi (-16.92%; P = 0.04 for Vmax and -18.73%; P = 0.02, for Vsucc, respectively). NO production was two-fold higher in the Endo compared with the Epi (P = 0.002) and interestingly, increasing NO concentration reduced Vmax. Mitochondrial H2O2 and LV ROS productions were significantly increased in Endo compared to Epi, citrate synthase activity and mitochondrial coupling being similar in the two layers.
  
  
  CONCLUSIONS
  LV mitochondrial respiration transmural gradient is likely related to NO and possibly ROS increased production in the sub-endocardium.
authors: Equipe d'Accueil 3072, Faculté de Médecine, Institut de Physiologie, Université de StrasbourgStrasbourg, France; Service de Chirurgie Cardiovasculaire, Pôle d'activité Médico-Chirurgicale Cardiovasculaire, Nouvel Hôpital Civil, CHRU de StrasbourgStrasbourg, France.
authors: Michel
authors: M
authors: Kindo
authors: Equipe d'Accueil 3072, Faculté de Médecine, Institut de Physiologie, Université de StrasbourgStrasbourg, France; Service de Chirurgie Cardiovasculaire, Pôle d'activité Médico-Chirurgicale Cardiovasculaire, Nouvel Hôpital Civil, CHRU de StrasbourgStrasbourg, France.
authors: Sébastien
authors: S
authors: Gerelli
authors: Equipe d'Accueil 3072, Faculté de Médecine, Institut de Physiologie, Université de StrasbourgStrasbourg, France; Service de Physiologie et d'Explorations Fonctionnelles, Pôle de Pathologie Thoracique, Nouvel Hôpital Civil, CHRU de StrasbourgStrasbourg, France.
authors: Jamal
authors: J
authors: Bouitbir
authors: Equipe d'Accueil 3072, Faculté de Médecine, Institut de Physiologie, Université de StrasbourgStrasbourg, France; Service de Chirurgie Cardiovasculaire, Pôle d'activité Médico-Chirurgicale Cardiovasculaire, Nouvel Hôpital Civil, CHRU de StrasbourgStrasbourg, France.
authors: Tam
authors: T
authors: Hoang Minh
authors: Equipe d'Accueil 3072, Faculté de Médecine, Institut de Physiologie, Université de StrasbourgStrasbourg, France; Service de Physiologie et d'Explorations Fonctionnelles, Pôle de Pathologie Thoracique, Nouvel Hôpital Civil, CHRU de StrasbourgStrasbourg, France.
authors: Anne-Laure
authors: AL
authors: Charles
authors: Service de Chirurgie Cardiovasculaire, Pôle d'activité Médico-Chirurgicale Cardiovasculaire, Nouvel Hôpital Civil, CHRU de Strasbourg Strasbourg, France.
authors: Jean-Philippe
authors: JP
authors: Mazzucotelli
authors: Equipe d'Accueil 3072, Faculté de Médecine, Institut de Physiologie, Université de StrasbourgStrasbourg, France; Service de Physiologie et d'Explorations Fonctionnelles, Pôle de Pathologie Thoracique, Nouvel Hôpital Civil, CHRU de StrasbourgStrasbourg, France.
authors: Joffrey
authors: J
authors: Zoll
authors: Equipe d'Accueil 3072, Faculté de Médecine, Institut de Physiologie, Université de StrasbourgStrasbourg, France; Service de Physiologie et d'Explorations Fonctionnelles, Pôle de Pathologie Thoracique, Nouvel Hôpital Civil, CHRU de StrasbourgStrasbourg, France.
authors: François
authors: F
authors: Piquard
authors: Equipe d'Accueil 3072, Faculté de Médecine, Institut de Physiologie, Université de StrasbourgStrasbourg, France; Service de Physiologie et d'Explorations Fonctionnelles, Pôle de Pathologie Thoracique, Nouvel Hôpital Civil, CHRU de StrasbourgStrasbourg, France.
authors: Bernard
authors: B
authors: Geny
keywords: energetic gradient; heart; mitochondria; nitric oxide; oxidative stress; transmural