Left ventricular assist device support normalizes left and right ventricular beta-adrenergic pathway properties
Left ventricular assist device support normalizes left and right ventricular beta-adrenergic pathway properties
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DOI：
10.1016/j.jacc.2004.11.042
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发表时间：
2005-03-01
影响因子：
24
通讯作者：
Burkhoff, D
中科院分区：
文献类型：
--
作者：
Klotz, S;Barbone, A;Burkhoff, D
我们假设左心室辅助装置（LVAD）逆转重构的某些方面可能不依赖于血流动力学因素，主要取决于神经激素环境的正常化。（提供给左心室[LV]）和正常化的神经激素环境方法从65名医学管理的移植患者（MED），30名LVAD支持的患者，结果MED组与MED组相比，肺动脉舒张压有降低的趋势（p < 0.01）和心输出量增加LVAD组（P < 0.001）; V-30（离体心室体积产生30 mm Hg，LVAD患者的心室大小指数）在LV中降低（p < 0.05），但在RV中没有显著变化。LVAD支持改善了在离体LV（开发力从6.3 +/- 0.6增加到18.5 +/- 4.4 mN/m（2），p < 0.01）和RV（开发力从10.9 +/- 2.0增加到20.5 +/- 3.1 mN/m（2）p < 0.05）小梁中响应β-肾上腺素能刺激的力产生。LVAD组左室和右室心肌β受体密度均显著高于对照组（P <0.01）。LVAD显著降低了RV和LV中RyR 2/钙释放通道的蛋白激酶A（PKA）过度磷酸化（p < 0.01）。结论：改善β-肾上腺素能反应性，RyR 2 PKA磷酸化正常化，增加beta-LVAD支持后左心室和右心室的肾上腺素能受体密度表明，神经激素环境在决定左心室和右心室的逆转重构中起主要作用。β-肾上腺素能通路。(C)2005年，美国心脏病学会基金会。
OBJECTIVES We hypothesized that some aspects of left ventricular assist device (LVAD) reverse remodeling could be independent of hemodynamic factors and would primarily depend upon normalization of neurohormonal milieu.BACKGROUND The relative contributions of LVAD-induced hemodynamic unloading (provided to the left ventricle [LV]) and normalized neurohormonal milieu (provided to LV and right ventricle [RV]) to reverse remodeling are not understood.METHODS Structural and functional characteristics were measured from hearts of 65 medically managed transplant patients (MED), 30 patients supported with an LVAD, and 5 nonfailing donor hearts not suitable for transplantation.RESULTS Compared with MED patients, diastolic pulmonary pressures trended lower (p < 0.01) and cardiac output higher (p < 0.001) in LVAD patients; V-30 (ex vivo ventricular volume yielding 30 mm Hg, an index of ventricular size) in LVAD patients was decreased in the LV (p < 0.05) but did not change significantly in RV. The LVAD support improved force generation in response to beta-adrenergic stimulation in isolated LV (increase in developed force from 6.3 +/- 0.6 to 18.5 +/- 4.4 mN/m(2), p < 0.01) and RV (increase in developed force, from 10.9 +/- 2.0 to 20.5 +/- 3.1 mN/m(2) p < 0.05) trabeculae. The LVAD patients had higher myocardial beta-adrenergic receptor density in LV (p < 0.01) and RV (p < 0.01). Protein kinase A (PKA) hyperphosphorylation of the ryanodine receptor 2 (RyR2)/calcium release channel was significantly reduced by LVAD in both RV and LV (p < 0.01).CONCLUSIONS Improved beta-adrenergic responsiveness, normalization of the RyR2 PKA phosphorylation, and increased beta-adrenergic receptor density in LV and RV after LVAD support suggest a primary role of neurohormonal environment in determining reverse remodeling of the beta-adrenergic pathway. (C) 2005 by the American College of Cardiology Foundation.