A cornerstone of heart failure treatment is not effective in experimental right ventricular failure.
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.


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-VEH rats.


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.
Center for Congenital Heart Diseases, Pediatric Cardiology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, The Netherlands. Electronic address: m.a.j.borgdorff@umcg.nl.
Marinus A
MA
Borgdorff
Beatrijs
B
Bartelds
Michael G
MG
Dickinson
Paul
P
Steendijk
Rolf M F
RM
Berger
D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D000077545:Eplerenone; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy* / Q000503:physiopathology
D013148:Spironolactone; D000077545:Eplerenone; D019808:Losartan
Fibrosis; Maladaptation; Pressure–volume loops; Pulmonary artery banding; RAAS system; Right ventricular failure