A cornerstone of heart failure treatment is not effective in experimental right ventricular failure
A cornerstone of heart failure treatment is not effective in experimental right ventricular failure
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DOI：
10.1016/j.ijcard.2013.08.102
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发表时间：
2013-11-05
影响因子：
3.5
通讯作者：
Berger, Rolf M. F.
中科院分区：
文献类型：
--
作者：
Borgdorff, Marinus A.;Bartelds, Beatrijs;Berger, Rolf M. F.
背景资料：在先天性心脏病和肺动脉高压患者中，由于压力负荷增加导致的右心室（RV）衰竭导致显著的发病率和死亡率。目前尚不清楚抑制肾素-血管紧张素-醛固酮系统（RAAS）（左心室衰竭治疗的基石）是否对RV衰竭有效。我们研究了醛固酮阻滞剂依普利酮+血管紧张素II受体阻滞剂氯沙坦（Ep/Lo）联合治疗对压力负荷增加所致RV衰竭模型中RV重塑和功能的影响。方法和结果：大鼠（n = 48）随机分为肺动脉结扎组（PAB）、假手术组和氯沙坦组（20 mg/kg/d）+依普利酮（100 mg/kg/d）治疗（Ep/Lo）或媒介物（VEH）。在第5周和第11周，或发生需要终止的临床RV衰竭症状时，通过超声心动图和压力-容积分析评估RV功能。PAB导致所有大鼠的RV衰竭，定义为心输出量减少、RV每搏输出量减少、RV舒张末期压增加和肝充血以及RV纤维化、肥大和毛细血管密度降低。在5/12只PAB-VEH大鼠中，临床RV衰竭需要终止。PAB大鼠RV中血管紧张素II 1型受体表达减少，表明局部RAAS激活。与PAB-VEH大鼠相比，Ep/Lo治疗PAB大鼠可显着降低动脉压，但对RV功能、重塑或生存无显着影响。结论：RAAS抑制并不能有益地影响慢性压力负荷引起的实验性RV衰竭。这具有高度临床相关性，因为它表明RV对RAAS抑制的反应可能与LV的反应根本不同。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Background: Right ventricular (RV) failure due to increased pressure load causes significant morbidity and mortality in patients with congenital heart diseases and pulmonary arterial hypertension. It is unknown whether renin-angiotensin-aldosterone-system (RAAS) inhibition (the cornerstone of left ventricular failure treatment) is effective in RV failure. We investigated the effects of combination treatment of aldosterone-blocker eplerenone + angiotensin II receptor blocker losartan (Ep/Lo) on RV remodeling and function in a model of RV failure due to increased pressure load.Methods and results: Rats (n = 48) were randomized for pulmonary artery banding (PAB) or sham surgery and for losartan (20 mg/kg/d) + eplerenone (100 mg/kg/d) treatment (Ep/Lo) or vehicle (VEH). RV function was assessed by echocardiography and pressure-volume analysis at 5 and 11 weeks, or at the occurrence of clinical RV failure symptoms necessitating termination.PAB resulted in RV failure in all rats, as defined by reduced cardiac output, RV stroke volume, increased RV end diastolic pressure and liver congestion as well as RV fibrosis, hypertrophy and reduced capillary density. Clinical RV failure necessitated termination in 5/12 PAB-VEH rats. Angiotensin II type 1-receptor expression in the RV was reduced in PAB rats indicating local RAAS activation. Treatment of PAB rats with Ep/Lo significantly lowered arterial pressures, but had no significant effect on RV function, remodeling or survival compared to PAB-VEHrats.Conclusions: RAAS inhibition does not beneficially affect experimental RV failure due to chronic pressure load. This is of high clinical relevance, because it indicates that the RV response to RAAS inhibition might fundamentally differ from that of the LV. (C) 2013 Elsevier Ireland Ltd. All rights reserved.