Alterations in the determinants of diastolic suction during pacing tachycardia

Alterations in the determinants of diastolic suction during pacing tachycardia
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DOI:
10.1161/01.res.87.3.235
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发表时间:
2000-08-04
影响因子:
20.1
通讯作者:
LeWinter, MM
LeWinter, MM
中科院分区:
医学1区
文献类型:
--
作者:
Bell, SP;Nyland, L;LeWinter, MM

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在心肌细胞中,负责弹性回缩的恢复力(RF)的产生涉及肌节蛋白Titin的变形以及松弛长度以下的缩短。在左心室(LV)水平,反冲和吸力充盈需要收缩到低于平衡容量(VEQ)的收缩末期容量(ESV),以及大范围的变形,例如扭转或扭转。人们对RFS和衰竭脑室的抽吸知之甚少。我们对有过2周起搏心动过速(PT)的开胸犬和对照组进行了吸力决定因素的比较。为了评估LV收缩到Veq以下的能力,我们使用伺服马达夹住左房压力并产生非充盈舒张期,允许测量不同容量的完全松弛压力。我们用声学显微镜对扭转进行了定量,还测定了N2B/N2BA、肌动蛋白亚型和总肌球蛋白与肌球蛋白重链(MHC)蛋白的跨壁比率。PT组LV不收缩到Veq以下,即使容量明显减少(EDP,1~2 mm Hg),而对照组当EDP小于5 mm Hg时,ESV小于Veq。在PT组,收缩和舒张期扭转速率都降低,并且在跨壁肌动蛋白亚型和肌动蛋白/MHC比率上有夸大的变化,这与心内膜下心肌中更具延展性的N2BA的存在是一致的。因此,在PT中,LV水平的吸力决定因素明显受损。改变的跨壁肌动蛋白亚型梯度与RFS的减少是一致的,并可能有助于这些发现。
In cardiomyocytes, generation of restoring forces (RFs) responsible for elastic recoil involves deformation of the sarcomeric protein titin in conjunction with shortening below slack length. At the left ventricular (LV) level, recoil and filling by suction require contraction to an end-systolic volume (ESV) below equilibrium volume (Veq) as well as large-scale deformations, for example, torsion or twist. Little is known about RFs and suction in the failing ventricle. We undertook a comparison of determinants of suction in open-chest dogs previously subjected to 2 weeks of pacing tachycardia (PT) and controls. To assess the ability of the LV to contract below Veq, we used a servomotor to clamp left atrial pressure and produce nonfilling diastoles, allowing measurement of fully relaxed pressure at varying volumes. We quantified twist with sonomicrometry, We also assessed transmural ratios of N2B to N2BA titin isoforms and total titin to myosin heavy chain (MHC) protein. In PT, the LV did not contract below Veq, even with marked reduction of volume (end-diastolic pressure [EDP], 1 to 2 mm Hg), whereas in controls ESV was less than Veq when EDP was less than approximate to 5 mm Hg. In PT, both systolic twist and diastolic untwisting rate were reduced, and there was exaggerated transmural variation in titin isoform and titin-to-MHC ratios, consistent with the more extensible N2BA being present in larger amounts in the subendocardium. Thus, in PT, determinants of suction at the level of the LV are markedly impaired. The altered transmural titin isoform gradient is consistent with a decrease in RFs and may contribute to these findings.