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

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• 作者：Gerrina Ruiter ; MD^a ; ^b ; Yeun Ying Wong ; MD^a ; ^b ; Frances S. de Man ; PhD^a ; M. Louis Handoko ; MD ; PhD^a ; ^b ; Richard T. Jaspers ; PhD^c ; Pieter E. Postmus ; MD ; PhD^a ; Nico Westerhof ; PhD^b ; Hans W.M. Niessen ; MD ; PhD^d ; Willem J. van der Laarse ; PhD^b ; Anton Vonk-Noordegraaf ; MD ; PhD^a ; ^{a.vonk@vumc.nl}
• 关键词：right heart failure ; myoglobin ; capillaries ; oxygen supply ; oxygen diffusion
• 刊名：The Journal of Heart and Lung Transplantation
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：32
• 期：2
• 页码：231-240
• 全文大小：1004 K

文摘

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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.