Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
Am J Physiol Lung Cell Mol Physiol. 2012 Dec 15;303(12):L1070-8. doi: 10.1152/ajplung.00135.2012. Epub 2012 Sep 7.
We previously demonstrated that diaphragm muscle weakness is present in experimental pulmonary arterial hypertension (PH). However, the nature of this diaphragm weakness is still unknown. Therefore, the aim of this study was to investigate whether changes at the sarcomeric level contribute to diaphragm weakness in PH. For this purpose, in control rats and rats with monocrotaline-induced PH, contractile performance and myosin heavy chain content of demembranated single diaphragm fibers were determined. We observed a reduced maximal tension of 20% (P < 0.05), whereas tension cost was preserved in type 2X and 2B diaphragm fibers in PH compared with control. The reduced maximal tension was associated with a reduction of force generated per half-sarcomeric myosin heavy chain content. Additionally, reduced Ca(2+) sensitivity of force generation was found in type 2X fibers compared with control, which could exacerbate diaphragm muscle weakness at submaximal activation. No changes in maximal tension and Ca(2+) sensitivity of force generation were observed in fibers from the nonrespiratory extensor digitorum longus muscle. Together, these findings indicate that diaphragm weakness in PH is at least partly caused by sarcomeric dysfunction, which appears to be specific for the diaphragm.
我们之前的研究表明，实验性肺动脉高压（PH）存在膈肌肌肉无力。然而，这种膈肌无力的性质尚不清楚。因此，本研究旨在探讨肌节水平的变化是否导致 PH 中的膈肌无力。为此，在对照大鼠和单硝酸异山梨酯诱导的 PH 大鼠中，测定了去膜单膈肌纤维的收缩性能和肌球蛋白重链含量。我们观察到最大张力降低了 20%（P < 0.05），而 PH 中的 2X 型和 2B 型膈肌纤维的张力消耗保持不变。最大张力的降低与每个半肌球蛋白重链含量产生的力的减少有关。此外，与对照组相比，2X 型纤维的力生成 Ca(2+)敏感性降低，这可能会加剧亚最大激活时的膈肌肌肉无力。来自非呼吸伸趾长肌的纤维中未观察到最大张力和力生成 Ca(2+)敏感性的变化。综上所述，这些发现表明 PH 中的膈肌无力至少部分是由肌节功能障碍引起的，这种功能障碍似乎是膈肌特有的。
