title: Right ventricular oxygen supply parameters are decreased in human and experimental pulmonary hypertension.
abstract: BACKGROUND
  In pulmonary arterial hypertension (PAH), high right ventricular (RV) power output requires increased myocardial oxygen consumption. Oxygen supply, however, does not increase in proportion. It is unknown what cellular mechanisms underlie this lack of adaptation. We therefore determined oxygen supply parameters in RV tissue slices of deceased PAH patients and compared them with RV tissue of patients who died from left ventricular myocardial infarction (MI). Because autopsy tissue only reflects end-stage disease, rat models with stable and progressive pulmonary hypertension (PH) were studied as well.
  
  
  METHODS
  Myocardial tissue of 10 PAH and 10 MI patients was collected at autopsy. In rats, stable PH (n = 6) and progressive PH (n = 6) was induced by 40 or 60 mg/kg monocrotaline, respectively. Six rats were used as controls.
  
  
  RESULTS
  RV cardiomyocyte cross-sectional area was strongly increased in PAH compared with MI patients (p < 0.001), whereas capillary density decreased (p < 0.01). Rat data showed similar RV hypertrophy in stable and progressive PH, and RV capillary density was decreased in both (p < 0.01 and p < 0.0001 vs control rats, respectively). RV myoglobin protein content and functional concentration were reduced in both human and rat PH RVs. In rats, this results from a lack of increase in myoglobin mRNA transcription per cardiomyocyte nucleus.
  
  
  CONCLUSIONS
  All measured cellular oxygen supply parameters are decreased in the failing human and rat pulmonary hypertensive RV. In contrast to stable PH rats, compensatory adaptations do not occur in end-stage PAH, despite higher myocardial oxygen consumption.
authors.affiliation: Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Gerrina
authors.initials: G
authors.lastname: Ruiter
authors.forename: Yeun
authors.initials: Y
authors.lastname: Ying Wong
authors.forename: Frances S
authors.initials: FS
authors.lastname: de Man
authors.forename: M
authors.initials: M
authors.lastname: Louis Handoko
authors.forename: Richard T
authors.initials: RT
authors.lastname: Jaspers
authors.forename: Pieter E
authors.initials: PE
authors.lastname: Postmus
authors.forename: Nico
authors.initials: N
authors.lastname: Westerhof
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van der Laarse
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk-Noordegraaf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004195:Disease Models, Animal; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000378:metabolism*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009211:Myoglobin / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D016278:Ventricular Function, Right / Q000502:physiology*
chemical_list: D009211:Myoglobin; D042461:Vascular Endothelial Growth Factor A