Mechanical unloading during left ventricular assist device support increases left ventricular collagen cross-linking and myocardial stiffness
Mechanical unloading during left ventricular assist device support increases left ventricular collagen cross-linking and myocardial stiffness
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DOI：
10.1161/circulationaha.104.515106
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发表时间：
2005-07-19
期刊：
影响因子：
37.8
通讯作者：
Burkhoff, D
中科院分区：
文献类型：
--
作者：
Klotz, S;Foronjy, RF;Burkhoff, D
背景-左心室辅助装置（LVAD）诱导衰竭心脏的逆向重构，除了细胞外基质，其表现出额外的病理生理学变化，尽管其机制和功能后果尚不清楚。方法和结果-心脏移植时从不需要LVAD支持的特发性扩张型心肌病（DCM）患者获得（n = 30），需要LVAD支持的患者（n = 16; LVAD持续时间，145 +/- 33天）和5例非衰竭心脏。测量左（LV）和右心室（RV）离体压力-容积关系，并测定心室和心肌硬度常数。测定心肌组织总胶原和交联胶原、I型和III型胶原、MMP-1、MMP-9、TIMP-1和血管紧张素（Ang）I和II含量。与无LVAD的DCM相比，LVAD后左室大小、质量和心肌细胞直径均减小（P < 0.05）。与非衰竭心脏相比，DCM中总胶原和交联胶原以及I型胶原与III型胶原的比例增加，并且在LVAD后进一步增加（与DCM和非衰竭心脏相比，P < 0.05）。同时，随着LVAD的增加，心室和心肌硬度增加。MMP-1与TIMP-1的比值在DCM中增加，并且在LVAD后几乎正常化，有利于减少胶原降解。组织Ang I和II也在LVAD期间增加。LVAD支持心脏的RV与DCM相比没有显著变化。结论- LVAD支持增加LV胶原交联和I型胶原与III型胶原的比率，这与心肌硬度增加有关。降低的组织MMP-1与TIMP-1比率（降低的降解）和增加的Ang水平（合成的刺激物）可能是这些变化的机制。对RV缺乏显著影响表明LV的血流动力学卸载（不提供给RV）可能是调节这些细胞外基质变化的主要因素。
Background - Left ventricular assist devices (LVADs) induce reverse remodeling of the failing heart except for the extracellular matrix, which exhibits additional pathophysiological changes, although their mechanisms and functional consequences are unknown.Methods and Results - Hearts were obtained at transplant from patients with idiopathic dilated cardiomyopathy (DCM) not requiring LVAD support ( n = 30), patients requiring LVAD support ( n = 16; LVAD duration, 145 +/- 33 days), and 5 nonfailing hearts. Left (LV) and right ventricular ( RV) ex vivo pressure-volume relationships were measured, and chamber and myocardial stiffness constants were determined. Myocardial tissue content of total and cross-linked collagen, collagen types I and III, MMP-1, MMP-9, TIMP-1, and angiotensin (Ang) I and II were measured. LV size, mass, and myocyte diameter decreased after LVAD compared with DCM without LVAD ( P < 0.05). Total and cross-linked collagen and ratio of type I to III collagen increased in DCM compared with nonfailing hearts and increased further after LVAD ( P < 0.05 versus DCM and nonfailing). Concomitantly, chamber and myocardial stiffness increased with LVAD. The ratio of MMP-1 to TIMP-1 increased in DCM and almost normalized after LVAD, favoring decreased collagen degradation. Tissue Ang I and II also increased during LVAD. There was no significant change in the RV of LVAD-supported heart compared with DCM.Conclusions - LVAD support increases LV collagen cross- linking and the ratio of collagen type I to III, which is associated with increased myocardial stiffness. Decreased tissue MMP-1 - to - TIMP-1 ratio ( decreased degradation) and increased Ang levels ( stimulants of synthesis) are likely mechanisms for these changes. Lack of significant effects on the RV suggest that hemodynamic unloading of the LV ( not provided to the RV) might be the primary factor that regulates these extracellular matrix changes.