Key result
Adding atenolol to spironolactone further improved histological and electrical remodeling in rats with heart failure (baseline LVEDP 32 ± 3 mm Hg) compared to spironolactone alone.
Why the study?
Does the addition of atenolol to spironolactone modify the beneficial effects of spironolactone on ventricular histological and electrical remodeling in a rat model of severe heart failure?
RCT (n=55)
Randomized into 5 groups
Does the addition of atenolol to spironolactone modify the beneficial effects of spironolactone on ventricular histological and electrical remodeling in a rat model of severe heart failure?
In a rat model of post-MI heart failure, adding a beta-blocker to an aldosterone antagonist further improved histological and electrical ventricular remodeling.
Answers are grounded in this paper and cite their sources.
Suggests additive remodeling benefits in severe HF models; leaves open clinical translation to patients.
BACKGROUND: Aldosterone antagonists (AAs) have beneficial effects on ventricular histological and electrical remodeling and improve noradrenaline uptake. Adding an AA to a beta-blocker (BB) further improves cardiac mortality in heart failure patients. We investigated if adjunction of a BB modifies beneficial effects of spironolactone on different parameters of the ventricular remodeling. METHODS: A severe myocardial infarction (MI) was produced in rats. Three months after surgery, left ventricular (LV) function was assessed by echocardiography. Fifty-five rats with heart failure were then randomized in 5 groups: sham, MI, and MI treated for 4 weeks with spironolactone (10 mg·kg·d), atenolol (1 mg·kg·d), or both. Holter transducers were implanted to record 24-hour ventricular electrical parameters, mean cycle length (RR) and SD of RR. Before killing, invasive left ventricular end diastolic pressure (LVEDP) was recorded. LV samples were used for histological analysis and catecholamine assay. RESULTS: Rats with MI had significantly increased LVEDP (32 ± 3 vs. 14 ± 1 mm Hg), LV, collagen content (5.8% ± 1.4% vs. 3.6% ± 0.7%), ventricular premature complexes (2.5 10 ± 10 vs. 30 ± 13), and decreased meanRR (164 ± 2 vs. 169 ± 1 milliseconds) and SDRR (3.9 ± 0.2 vs. 5.4 ± 0.2 milliseconds) compared with sham. At nonhypotensive doses, spironolactone and atenolol similarly improved LVEDP. Compared with MI, although spironolactone significantly decreased ventricular premature complexes, LV collagen and noradrenaline contents, and improved meanRR and SDRR, atenolol had effects only on meanRR and SDRR. Addition of atenolol to spironolactone further improved spironolactone effects on all these parameters. CONCLUSIONS: AA improved, independently of the cardiac function, histological and electrical remodeling after MI. A BB added to an AA did not blunt these beneficial effects; furthermore, it improved these effects related to spironolactone.
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Milliez et al. (2012) conducted an RCT in Heart failure post-myocardial infarction (rats) (n=55). Spironolactone, atenolol, or both vs. Sham and untreated myocardial infarction was evaluated on Ventricular histological and electrical remodeling (LVEDP, LV collagen, VPCs, meanRR, SDRR). Adding atenolol to spironolactone further improved histological and electrical remodeling in rats with heart failure (baseline LVEDP 32 ± 3 mm Hg) compared to spironolactone alone.
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