Spironolactone reduces fibrosis of dilated atria during heart failure in rats with myocardial infarction.
OBJECTIVE
Congestive heart failure (CHF) is associated with severe structural changes of atria, contributing to impaired atrial function and the risk of arrhythmia. This study investigated the effects of CHF treatments on atrial remodelling.


RESULTS
Three months after myocardial infarction (MI), rats were treated for 1 month with spironolactone, lisinopril, or atenolol alone or in combination. Echocardiography-Doppler tissue imaging, haemodynamic measurements, and 24-h Holter monitoring were used to characterize the cardiomyopathy. Atrial fibrosis was quantified with Picrosirius Red staining. Left atrial diameter was increased (5.8+/-0.6 mm in MI vs. 3.6+/-0.3 mm in sham; P<0.0001), as was atrial fibrosis (26.7+/-3.8% in MI vs. 10.5+/-2.2% in sham; P<0.0001), which correlated with left ventricular (LV) dysfunction after 3 months of MI. P-wave duration was also increased and premature atrial beats were frequent on the 24-h electrocardiogram. Similar improvements in LV dysfunction were observed after 1 month of spironolactone, ACE-inhibitor, or beta-blocker therapy alone or in combination. Atrial hyperexcitability was reduced by all the treatments, but only spironolactone attenuated atrial fibrosis and reduced P-wave duration.


CONCLUSIONS
Atrial fibrosis caused by chronic CHF is reduced by spironolactone.
Milliez
Paul
P
Centre de Recherches Cardiovasculaires Inserm Lariboisière--Unité U689, Paris, France.
Deangelis
Noeleen
N
Rucker-Martin
Catherine
C
Leenhardt
Antoine
A
Vicaut
Eric
E
Robidel
Estelle
E
Beaufils
Philippe
P
Delcayre
Claude
C
Hatem
Stéphane N
SN
D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000209:etiology; D005355:Fibrosis; D006325:Heart Atria / Q000473:pathology; D006333:Heart Failure / Q000473:pathology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone