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

    Research output: Contribution to JournalArticleAcademicpeer-review

    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. © 2013 International Society for Heart and Lung Transplantation.
    Original languageEnglish
    Pages (from-to)231-240
    JournalJournal of Heart and Lung Transplantation
    Volume32
    Issue number2
    DOIs
    Publication statusPublished - 2013

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