Myocardial Atrophy and Chronic Mechanical Unloading of the Failing Human Heart

被引：71

作者：

Diakos, Nikolaos A. ^{[1
,2
,3
]}

Selzman, Craig H. ^{[1
,2
,3
]}

Sachse, Frank B. ^{[4
]}

Stehlik, Josef ^{[1
,2
]}

Kfoury, Abdallah G. ^{[1
,2
]}

Wever-Pinzon, Omar ^{[1
,2
]}

Catino, Anna ^{[1
,2
]}

Alharethi, Rami ^{[1
,2
]}

Reid, Bruce B. ^{[1
,2
]}

Miller, Dylan V. ^{[1
,2
,5
]}

Salama, Mohamed ^{[5
]}

Zaitsev, Alexey V. ^{[4
]}

Shibayama, Junko ^{[4
]}

Li, Hui ^{[4
]}

Fang, James C. ^{[1
,2
]}

Li, Dean Y. ^{[3
]}

Drakos, Stavros G. ^{[1
,2
,3
]}

机构：

[1] Univ Utah, Utah Transplantat Affiliated Hosp UTAH Cardiac Tr, Div Cardiovasc Med, Hlth Sci Ctr,Intermt Med Ctr,Vet Adm Salt Lake Ci, Salt Lake City, UT 84132 USA

[2] Univ Utah, Utah Transplantat Affiliated Hosp UTAH Cardiac Tr, Div Cardiothorac Surg, Hlth Sci Ctr,Intermt Med Ctr,Vet Adm Salt Lake Ci, Salt Lake City, UT 84132 USA

[3] Univ Utah, Program Mol Med, Salt Lake City, UT 84132 USA

[4] Univ Utah, Nora Eccles Harrison Cardiovasc Res & Training In, Salt Lake City, UT 84132 USA

[5] Univ Utah, Dept Pathol, Sch Med, ARUP Reference Lab, Salt Lake City, UT 84132 USA

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2014年 / 64卷 / 15期

基金：

美国国家卫生研究院;

关键词：

left ventricular assist device; mechanical unloading; myocardial atrophy; VENTRICULAR ASSIST DEVICE; CONTINUOUS-FLOW; HETEROTOPIC TRANSPLANTATION; RAT-HEART; CLENBUTEROL; FAILURE; MODEL; HYPERTROPHY; SUPPORT; BRIDGE;

D O I：

10.1016/j.jacc.2014.05.073

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND In animal models of heterotopic transplantation, mechanical unloading of the normal, nonhypertrophic heart results in atrophy. Primarily on the basis of these animal data, the notion that chronic left ventricular assist device (LVAD)-induced unloading will result in atrophy has dominated the clinical heart failure field, and anti-atrophic drugs have been used to enhance the cardiac recovery potential observed in some LVAD patients. However, whether unloading-induced atrophy in experimental normal heart models applies to failing and hypertrophic myocardium in heart failure patients unloaded by continuous-flow LVADs has not been studied. OBJECTIVES The study examined whether mechanical unloading by continuous-flow LVAD leads to myocardial atrophy. METHODS We prospectively examined myocardial tissue and hemodynamic and echocardiographic data from 44 LVAD patients and 18 untransplanted normal donors. RESULTS Cardiomyocyte size (cross-sectional area) decreased after LVAD unloading from 1,238 +/- 81 mu m(2) to 1,011 +/- 68 mm(2) (p = 0.001), but not beyond that of normal donor hearts (682 +/- 56 mu m(2)). Electron microscopy ultrastructural evaluation, cardiomyocyte glycogen content, and echocardiographic assessment of myocardial mass and left ventricular function also did not suggest myocardial atrophy. Consistent with these findings, t-tubule morphology, cytoplasmic penetration, and distance from the ryanodine receptor were not indicative of ongoing atrophic remodeling during LVAD unloading. Molecular analysis revealed no up-regulation of proatrophic genes and proteins of the ubiquitin proteasome system. CONCLUSIONS Structural, ultrastructural, microstructural, metabolic, molecular, and clinical functional data indicated that prolonged continuous-flow LVAD unloading does not induce hypertrophy regression to the point of atrophy and degeneration. These findings may be useful in designing future investigations that combine LVAD unloading and pharmaceutical therapies as a bridge to recovery of the failing heart. (C) 2014 by the American College of Cardiology Foundation.

引用

页码：1602 / 1612

页数：11

共 44 条

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