Abstract
Introduction: Mineralocorticoid receptor antagonists (MRAs) are effective in reducing left ventricle remodeling and sudden death after acute myocardial infarction (AMI). Objectives: MRAs in vitro display cardioprotective effects, independent of MR; however, it is unknown whether the rapid effects of MRAs are cardioprotective in vivo. This study evaluated the acute effects of spironolactone and eplerenone in the first minutes of AMI. Methods: Wistar Rats, submitted or not to bilateral adrenalectomy, were treated orally with spironolactone (20 mg/kg) or eplerenone (10 mg/kg), and submitted to the left coronary ligation, under anesthesia. Electrocardiogram (ECG) recordings were obtained to evaluate ST-T segment, QT, and QTc intervals. Arterial pressure was also measured before (baseline) and after coronary ligation. Results: Spironolactone or eplerenone given, one hour before coronary ligation, prevented ST-T segment elevation in adrenalectomized and non-adrenalectomized. QT interval analysis showed that MRAs prevented its prolongation after coronary ligation. QT and QTc intervals remained similar to baseline and were smaller than the values displayed by the non-treated group. Animals treated with spironolactone, regardless of adrenalectomy, showed a 3-fold reduced mortality rates compared to the control group. Conclusion: MRAs display acute cardioprotective effects in early phase of AMI, which are independent of aldosterone.
Highlights
Mineralocorticoid receptor antagonists (MRAs) are effective in reducing left ventricle remodeling and sudden death after acute myocardial infarction (AMI)
We evaluated whether MRAs, spironolactone or eplerenone, are cardioprotective during early phase of ischemia in a model of acute cardiac ischemia induced by coronary ligation in rats
No difference was observed between the groups submitted solely to coronary ligation (2 ± 0.6 ng/dl) compared to groups submitted to the same procedure and treated with either spironolactone (1 ± 0.7 ng/dl) or eplerenone (1 ± 0.5 ng/dl)
Summary
Mineralocorticoid receptor antagonists (MRAs) are effective in reducing left ventricle remodeling and sudden death after acute myocardial infarction (AMI). The mineralocorticoid receptor antagonists (MRA), spironolactone and eplerenone, are effective to treat patients with mild or chronic heart failure (HF) and left ventricular (LV) dysfunction after AMI, mainly by reducing morbidity and mortality (Pitt et al, 2003; Zannad et al, 2010). The most comprehend mechanism of action of aldosterone in the heart is the genomic (slow) pathway, which is mediated by cytosolic intracellular MR receptors. This process involves translocation of aldosterone-MR complex to nucleus that acts as a transcriptional regulator that leads to protein synthesis (Rogerson et al, 2004)
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