title: Time course of differential mitochondrial energy metabolism adaptation to chronic hypoxia in right and left ventricles.
abstract: OBJECTIVE
  The present study was designed to characterize mitochondrial adaptation to chronic hypoxia (CH) in the rat heart. Mitochondrial energy metabolism was differentially examined in both left and right ventricles since CH selectively triggers pulmonary hypertension and right ventricular hypertrophy.
  
  
  METHODS
  Rats were exposed to a hypobaric environment for 2 or 3 weeks and compared with rats maintained in a normoxic environment. Oxidative capacity (oxygen consumption and ATP synthesis) was measured in saponin-skinned fibers with glutamate or palmitoyl carnitine as substrates. Enzymatic activities of mitochondrial respiratory chain complexes were measured on tissue homogenates. Morphometric analysis of mitochondria was performed on electron micrographs. Mitochondrial DNA was quantified using Southern blot analysis.
  
  
  RESULTS
  Whereas oxidative capacity of both ventricles was decreased following 21 days of CH, oxygen consumption and ATP synthesis was maintained with the glutamate substrate in the right ventricle following 14 days of CH. As for the oxidative capacity, enzyme activities were decreased only in the left ventricle following 14 days of CH and in both ventricles following 21 days of CH. These functional alterations were associated with an increase in numerical density and a decrease in size of mitochondria without a change in volume density in both ventricles. Finally, 21 days of CH also decreased the ratio of mitochondrial DNA to nuclear DNA in both ventricles.
  
  
  CONCLUSIONS
  CH alters morphometry and function of mitochondria in the heart, but this effect is delayed in the right compared to the left ventricle, suggesting some adaptive processes at the onset of right ventricular hypertrophy.
authors.affiliation: Laboratoire d'anesthésiologie, E.A. Physiologie Mitochondriale, Université Victor Segalen Bordeaux 2, 33076 Bordeaux Cedex, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Nouette-Gaulain
authors.forename: Monique
authors.initials: M
authors.lastname: Malgat
authors.forename: Christophe
authors.initials: C
authors.lastname: Rocher
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Savineau
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mazat
authors.forename: Francois
authors.initials: F
authors.lastname: Sztark
mesh_terms: D000251:Adenosine Triphosphatases / Q000096:biosynthesis; D000818:Animals; D015139:Blotting, Southern / Q000379:methods; D002467:Cell Nucleus / Q000648:ultrastructure; D002908:Chronic Disease; D004247:DNA / Q000648:ultrastructure; D004272:DNA, Mitochondrial / Q000648:ultrastructure; D004734:Energy Metabolism; D006352:Heart Ventricles; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000648:ultrastructure; D010085:Oxidative Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D004272:DNA, Mitochondrial; D004247:DNA; D000251:Adenosine Triphosphatases