射血分数保留的早期心力衰竭犬模型中的左心房重塑与房室耦联

Left Atrial Remodeling and Atrioventricular Coupling in a Canine Model of Early Heart Failure With Preserved Ejection Fraction.

作者信息

Zakeri Rosita, Moulay Gilles, Chai Qiang, Ogut Ozgur, Hussain Saad, Takahama Hiroyuki, Lu Tong, Wang Xiao-Li, Linke Wolfgang A, Lee Hon-Chi, Redfield Margaret M

机构信息

From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (R.Z., G.M., Q.C., O.O., S.H., H.T., T.L., X.-L.W., H.-C.L., M.M.R.); and Department of Cardiovascular Physiology, Ruhr University Bochum, Germany (WA.L).

出版信息

Circ Heart Fail. 2016 Oct;9(10). doi: 10.1161/CIRCHEARTFAILURE.115.003238. Epub 2016 Oct 10.

DOI:10.1161/CIRCHEARTFAILURE.115.003238

PMID:27758811

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5082983/

Abstract

BACKGROUND

Left atrial (LA) compliance and contractility influence left ventricular stroke volume. We hypothesized that diminished LA compliance and contractile function occur early during the development of heart failure with preserved ejection fraction (HFpEF) and impair overall cardiac performance.

METHODS AND RESULTS

Cardiac magnetic resonance imaging, echocardiography, left ventricular and LA pressure-volume studies, and tissue analyses were performed in a model of early HFpEF (elderly dogs, renal wrap-induced hypertension, exogenous aldosterone; n=9) and young control dogs (sham surgery; n=13). Early HFpEF was associated with LA enlargement, cardiomyocyte hypertrophy, and enhanced LA contractile function (median active emptying fraction 16% [95% confidence interval, 13-24]% versus 12 [10-14]%, P=0.008; end-systolic pressure-volume relationship slope 2.4 [1.9-3.2]mm Hg/mL HFpEF versus 1.5 [1.2-2.2]mm Hg/mL controls, P=0.01). However, atrioventricular coupling was impaired and the curvilinear LA end-reservoir pressure-volume relationship was shifted upward/leftward in HFpEF (LA stiffness constant [β] 0.16 [0.11-0.18]mm Hg/mL versus 0.06 [0.04-0.10]mm Hg/mL controls; P=0.002), indicating reduced LA compliance. Impaired atrioventricular coupling and lower LA compliance correlated with lower left ventricular stroke volume. Total fibrosis and titin isoform composition were similar between groups; however, titin was hyperphosphorylated in HFpEF and correlated with β. LA microvascular reactivity was diminished in HFpEF versus controls. LA microvascular density tended to be lower in HFpEF and inversely correlated with β.

CONCLUSIONS

In early-stage hypertensive HFpEF, LA cardiomyocyte hypertrophy, titin hyperphosphorylation, and microvascular dysfunction occur in association with increased systolic and diastolic LA chamber stiffness, impaired atrioventricular coupling, and decreased left ventricular stroke volume. These data indicate that maladaptive LA remodeling occurs early during HFpEF development, supporting a concept of global myocardial remodeling.

摘要

背景

左心房（LA）顺应性和收缩性影响左心室每搏输出量。我们假设，在射血分数保留的心力衰竭（HFpEF）发展过程中，LA顺应性和收缩功能早期即出现减退，并损害整体心脏功能。

方法和结果

对早期HFpEF模型（老年犬，肾包囊诱导型高血压，外源性醛固酮；n = 9）和年轻对照犬（假手术；n = 13）进行心脏磁共振成像、超声心动图、左心室和LA压力-容积研究以及组织分析。早期HFpEF与LA扩大、心肌细胞肥大和LA收缩功能增强相关（中位主动排空分数16% [95%置信区间，13 - 24]% 对比12 [10 - 14]%，P = 0.008；收缩末期压力-容积关系斜率2.4 [1.9 - 3.2]mmHg/mL HFpEF对比1.5 [1.2 - 2.2]mmHg/mL对照组，P = 0.01）。然而，HFpEF中房室耦联受损，LA终末储备压力-容积关系曲线向上/向左移位（LA僵硬度常数[β] 0.16 [0.11 - 0.18]mmHg/mL对比0.06 [0.04 - 0.10]mmHg/mL对照组；P = 0.002），表明LA顺应性降低。房室耦联受损和LA顺应性降低与左心室每搏输出量降低相关。两组间总纤维化和肌联蛋白异构体组成相似；然而，HFpEF中肌联蛋白过度磷酸化且与β相关。与对照组相比，HFpEF中LA微血管反应性降低。HFpEF中LA微血管密度趋于降低且与β呈负相关。