Center for Congenital Heart Diseases, Pediatric Cardiology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, The Netherlands.
Int J Cardiol. 2013 Nov 5;169(3):183-9. doi: 10.1016/j.ijcard.2013.08.102. Epub 2013 Sep 7.
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.
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-VEH rats.
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.
由于压力负荷增加导致的右心室（RV）衰竭会使先天性心脏病和肺动脉高压患者的发病率和死亡率显著增加。目前尚不清楚肾素-血管紧张素-醛固酮系统（RAAS）抑制（左心室衰竭治疗的基石）是否对 RV 衰竭有效。我们研究了在压力负荷增加导致 RV 衰竭的模型中，醛固酮阻滞剂依普利酮+血管紧张素 II 受体阻滞剂洛沙坦（Ep/Lo）联合治疗对 RV 重构和功能的影响。
大鼠（n=48）随机分为肺动脉缩窄（PAB）或假手术组，以及洛沙坦（20 mg/kg/d）+依普利酮（100 mg/kg/d）治疗（Ep/Lo）或载体（VEH）组。通过超声心动图和压力-容积分析在 5 周和 11 周评估 RV 功能，或在出现需要终止的 RV 衰竭临床症状时进行评估。PAB 导致所有大鼠出现 RV 衰竭，表现为心输出量、RV 每搏量降低，RV 舒张末期压和肝淤血升高，以及 RV 纤维化、肥大和毛细血管密度降低。5/12 只 PAB-VEH 大鼠出现 RV 衰竭临床症状需要终止。RV 中的血管紧张素 II 型 1 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 大鼠可显著降低动脉压，但对 RV 功能、重构或存活率无显著影响。
RAAS 抑制对慢性压力负荷导致的实验性 RV 衰竭没有有益作用。这具有重要的临床意义，因为它表明 RV 对 RAAS 抑制的反应可能与 LV 根本不同。
