Klotz Stefan, Danser A H Jan, Foronjy Robert F, Oz Mehmet C, Wang Jie, Mancini Donna, D'Armiento Jeanine, Burkhoff Daniel
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
J Am Coll Cardiol. 2007 Mar 20;49(11):1166-74. doi: 10.1016/j.jacc.2006.10.071. Epub 2007 Mar 7.
We hypothesized that angiotensin-converting enzyme inhibition (ACE-I) during left ventricular assist device (LVAD) support in patients with end-stage heart failure prevents potentially deleterious effects on the extracellular matrix.
Left ventricular assist device-induced mechanical unloading increases myocardial collagen and stiffness and may contribute to the low rate of recovery.
Heart samples obtained before and after LVAD implantation were divided into groups depending on whether the patients received (n = 7) or did not receive (control; n = 15) ACE-I. At transplant, ex vivo pressure-volume relationships were measured and chamber and myocardial stiffness constants determined. Myocardial tissue content of angiotensin (Ang) I and II, matrix metalloproteinase (MMP)-1, tissue inhibitor of MMPs (TIMP)-1, and total and cross-linked collagen was measured.
Duration of support was comparable between ACE-I and control subjects (96 +/- 65 days vs. 109 +/- 22 days). Pre-LVAD Ang I and II and total and cross-linked collagen were similar between groups. Post-LVAD, Ang II was reduced in the ACE-I group but increased in control subjects (181 +/- 7 fmol/g vs. 262 +/- 41 fmol/g; p < 0.05). Similarly, cross-linked collagen decreased during LVAD support in the ACE-I group. Left ventricular (LV) mass and myocardial stiffness were lower in the ACE-I group. ACE-I normalized the LV and right ventricular (RV) MMP-1/TIMP-1 ratio. Collagen content and characteristics of the RV were not affected by ACE-I.
ACE-I therapy was associated with decreased Ang II, myocardial collagen content, and myocardial stiffness during LVAD support. This is the first demonstration of a pharmacologic therapy that can impact myocardial properties during mechanical unloading, and it could foster new lines of investigation in strategies of enhancing myocardial recovery during LVAD support.
我们假设，在终末期心力衰竭患者接受左心室辅助装置（LVAD）支持期间，使用血管紧张素转换酶抑制剂（ACE-I）可预防对细胞外基质的潜在有害影响。
LVAD引起的机械性卸载会增加心肌胶原蛋白和硬度，并可能导致恢复率较低。
根据患者是否接受（n = 7）或未接受（对照组；n = 15）ACE-I，将LVAD植入前后获取的心脏样本分组。在移植时，测量体外压力-容积关系，并确定心室和心肌硬度常数。测量心肌组织中血管紧张素（Ang）I和II、基质金属蛋白酶（MMP）-1、MMP组织抑制剂（TIMP）-1以及总胶原蛋白和交联胶原蛋白的含量。
ACE-I组和对照组的支持时间相当（96±65天对109±22天）。LVAD植入前，两组之间的Ang I和II以及总胶原蛋白和交联胶原蛋白相似。LVAD植入后，ACE-I组的Ang II减少，而对照组增加（181±7 fmol/g对262±41 fmol/g；p<0.05）。同样，ACE-I组在LVAD支持期间交联胶原蛋白减少。ACE-I组的左心室（LV）质量和心肌硬度较低。ACE-I使LV和右心室（RV）的MMP-1/TIMP-1比值正常化。ACE-I对RV的胶原蛋白含量和特性没有影响。
ACE-I治疗与LVAD支持期间Ang II减少、心肌胶原蛋白含量和心肌硬度降低有关。这是首次证明一种药物治疗可在机械性卸载期间影响心肌特性，并且它可能会促进LVAD支持期间增强心肌恢复策略的新研究方向。
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