Background and purpose: Suppression of the renin-angiotensin-aldosterone system can prevent atrial fibrillation (AF) by attenuating atrial structural remodelling but the role of aldosterone in AF prevention has not been investigated thoroughly. We explored whether the aldosterone antagonist, spironolactone, could improve atrial structural remodelling in long-term rapid pacing-induced AF. Experimental approach: Three groups of dogs were used, sham-operated, control and spironolactone-treated groups. Dogs in the control and spironolactone groups had right atrial pacing for 6 weeks. The spironolactone group was given spironolactone 1 week before and during the atrial pacing. After 6 weeks of pacing, atrial structural and functional changes were assessed by echocardiography, haemodynamic parameters by cardiac catheterization, histopathological changes by light and electron microscopy and cardiomyocyte apoptosis by TUNEL. Caspase-3, Bcl-2, bax, calpain I, calpastatin, matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinase (TIMP)-1 were analysed by immunohistochemistry and Western blotting. The inducibility and duration of AF were measured by atrial burst pacing. Key results: After atrial pacing, the proportion of TUNEL positive cells, myolysis, atrial fibrosis and dilatation were all significantly increased and these changes were inhibited by spironolactone. Spironolactone treatment reversed the increased expression of caspase-3, bax, calpain I and MMP-9 and the decreased level of Bcl-2, calpastatin and TIMP-1, induced by chronic atrial pacing. Also spironolactone prevented the increased inducibility and duration of AF, induced by tachypacing. Conclusions and implications: Treatment with spironolactone prevented myocardial apoptosis, myolysis, atrial fibrosis and dilatation, suggesting a possible beneficial effect of aldosterone antagonism on atrial structural remodelling in AF.

The cardioprotective effects of carvedilol were studied in a rat model of experimental autoimmune myocarditis (EAM). After immunization, rats were orally administered 10 mg/kg/day carvedilol (group C, n = 15) or a vehicle control (Group V, n = 12) for 3 weeks. On day 21, echocardiography and haemodynamic parameters, myocarditis areas, and cytokine concentrations were measured. Serum carvedilol concentrations ranged from 10.5 ± 2.6 to 31.7 ± 9.3 ng/ml over a 24 h period on day 20. Carvedilol decreased the myocarditis areas (23.07 ± 1.6 versus 33.65 ± 2.71%, P < 0.0001). The left ventricular fractional shortening and the absolute value of +dP/dt or –dP/dt were significantly higher in Group C. Heart rate, systolic blood pressure, left ventricular end‐diastolic pressure and central venous pressure were significantly lower in Group C. The serum and mRNA levels of interleukin (IL)‐1β (53.58 ± 6.42 versus 98.75 ± 6.53 pg/ml, P < 0.0001 and 0.298 ± 0.04 versus 0.818 ± 0.252, P < 0.0001, respectively) and TNF‐α (14.82 ± 1.95 versus 29.52 ± 3.7 pg/ml, P = 0.0008 and 0.088 ± 0.006 versus 0.168 ± 0.072, P = 0.0051, respectively) were markedly decreased, whereas IL‐10 (24.92 ± 2.94 versus 15.25 ± 3.13 pg/ml, P = 0.015 and 0.302 ± 0.022 versus 0.107 ± 0.02, P < 0.0001, respectively) and IL‐1 receptor antagonist (1.95 ± 0.28 versus 0.52 ± 0.10 pg/ml, P < 0.0001 and 0.112 ± 0.009 versus 0.051 ± 0.002, P < 0.0001, respectively) were markedly increased in the Group C. These results indicate that in rats carvedilol protects against EAM.