Right ventricular oxygen supply parameters are decreased in human and experimental pulmonary hypertension

G. Ruiter, Y.Y. Wong, F.S. de Man, M.L. Handoko, R.T. Jaspers, P.E. Postmus, N. Westerhof, H.W.M. Niessen, W.J. van der Laarse, A. Vonk Noordegraaf

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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.

Original languageEnglish
Pages (from-to)231-240
Number of pages10
JournalJournal of Heart and Lung Transplantation
Issue number2
Publication statusPublished - Feb 2013


  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Disease Models, Animal
  • Heart Failure
  • Heart Ventricles
  • Humans
  • Hypertension, Pulmonary
  • Journal Article
  • Middle Aged
  • Myocardial Infarction
  • Myocardium
  • Myocytes, Cardiac
  • Myoglobin
  • Oxygen Consumption
  • Rats
  • Research Support, Non-U.S. Gov't
  • Vascular Endothelial Growth Factor A
  • Ventricular Function, Right

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