Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands.
J Heart Lung Transplant. 2013 Feb;32(2):231-40. doi: 10.1016/j.healun.2012.09.025. Epub 2012 Nov 9.
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.
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.
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.
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.
在肺动脉高压（PAH）中，右心室（RV）高动力输出需要增加心肌耗氧量。然而，氧供应并没有成比例增加。目前尚不清楚是什么细胞机制导致了这种适应不良。因此，我们测定了已故 PAH 患者 RV 组织切片中的氧供应参数，并将其与因左心室心肌梗死（MI）而死亡的 RV 组织进行了比较。由于尸检组织仅反映终末期疾病，因此还研究了稳定和进行性肺动脉高压（PH）的大鼠模型。
在尸检时收集了 10 例 PAH 和 10 例 MI 患者的心肌组织。在大鼠中，分别用 40 或 60mg/kg 野百合碱诱导稳定 PH（n = 6）和进行性 PH（n = 6）。6 只大鼠作为对照组。
与 MI 患者相比，PAH 患者的 RV 心肌细胞横截面积明显增加（p < 0.001），而毛细血管密度降低（p < 0.01）。大鼠数据显示稳定和进行性 PH 均有类似的 RV 肥大，且两者的 RV 毛细血管密度均降低（分别为 p < 0.01 和 p < 0.0001 与对照大鼠相比）。在人 PH 和大鼠 PH RV 中，RV 肌红蛋白蛋白含量和功能浓度均降低。在大鼠中，这是由于每个心肌细胞核的肌红蛋白 mRNA 转录没有增加所致。
在衰竭的人 PH 和大鼠 PH RV 中，所有测量的细胞氧供应参数均降低。与稳定 PH 大鼠不同，尽管心肌耗氧量增加，但在终末期 PAH 中没有发生代偿性适应。
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