Mechanisms Involved in the Beneficial Effects of Spironolactone after Myocardial Infarction

Minicucci, Marcos F.; Santos, Priscila P.; Rafacho, Bruna Paola Murino; Gonçalves, Andréa; Silva, Renata A. C.; Chiuso-Minicucci, Fernanda; Azevedo, Paula Schmidt; Polegato, Bertha Furlan; Okoshi, Katashi; Pereira, Elenize Jamas; Paiva, Sérgio Alberto Rupp de; Zornoff, Leonardo A. M.

doi:10.1371/journal.pone.0076866

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…This refers to increase in infarct zone and apoptosis of cardiomyocytes, after 30 min of ischemia followed by 2.5 hours of reperfusion period. These detrimental cardiac effects were reversed by MR inverse agonist spironolactone acting as a MR inverse agonist at a low dose of 10nM (Minicucci et al 2013). In line with these results were also the findings of Marcos et al, who highlighted the spironolactone induced attenuation of cardiac remodeling after AMI in an animal model.…”

Section: Preclinical Datasupporting

confidence: 81%

The role of aldosterone inhibitors in cardiac ischemia–reperfusion injury

Dragasevic

Jakovljević

Živković

et al. 2021

Can. J. Physiol. Pharmacol.

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Myocardial ischaemia-reperfusion (I/R) injury is well known term for paradoxal exacerbation of cellular destruction and dysfunction, after the restoration of blood flow to previously ischaemic heart. A vast number of studies that has demonstrated the role of mineralocorticoids in cardiovascular diseases is based on the use of pharmacological mineralocorticoid receptor antagonists (MRA) such as spironolactone and eplerenone. This review paper aimed to summarize current knowledge on the effects of MR antagonists on myocardial I/R injury, as well as post-infarction remodeling. Animal models, predominantly Langendorff technique and left anterior descending coronary artery occlusion (LAD) have confirmed the potency of MRA as preconditioning and postconditioning agents in limiting infarct size and postinfarction remodeling. Several preclinical studies in rodents have established and proved possible mechanisms of cardioprotection by MRA, such as reduction of oxidative stress, reduction of inflammation and apoptosis, therefore limiting infarct zone. However, the results of some clinical trials are inconsistent with these results since they reported no benefit of MRA in acute myocardial infarction. Due to this, further studies and the results of on-going clinical trials regarding MRA administration in patients with acute myocardial infarction are being awaited with great interest.

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Section: Preclinical Datasupporting

confidence: 81%

The role of aldosterone inhibitors in cardiac ischemia–reperfusion injury

Dragasevic

Jakovljević

Živković

et al. 2021

Can. J. Physiol. Pharmacol.

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“…Diastolic function was assessed by the E/A ratio, the E-wave deceleration time (EDT) and the Isovolumic Relaxation Time Adjusted for Heart Rate (IVRT/HR). 22 , 23 …”

Section: Methodsmentioning

confidence: 99%

Association between Functional Variables and Heart Failure after Myocardial Infarction in Rats

Polegato¹,

Minicucci²,

Azevedo³

et al. 2016

Arquivos Brasileiros De Cardiologia

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BackgroundHeart failure prediction after acute myocardial infarction may have important clinical implications.ObjectiveTo analyze the functional echocardiographic variables associated with heart failure in an infarction model in rats.MethodsThe animals were divided into two groups: control and infarction. Subsequently, the infarcted animals were divided into groups: with and without heart failure. The predictive values were assessed by logistic regression. The cutoff values predictive of heart failure were determined using ROC curves.ResultsSix months after surgery, 88 infarcted animals and 43 control animals were included in the study. Myocardial infarction increased left cavity diameters and the mass and wall thickness of the left ventricle. Additionally, myocardial infarction resulted in systolic and diastolic dysfunction, characterized by lower area variation fraction values, posterior wall shortening velocity, E-wave deceleration time, associated with higher values of E / A ratio and isovolumic relaxation time adjusted by heart rate. Among the infarcted animals, 54 (61%) developed heart failure. Rats with heart failure have higher left cavity mass index and diameter, associated with worsening of functional variables. The area variation fraction, the E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate were functional variables predictors of heart failure. The cutoff values of functional variables associated with heart failure were: area variation fraction < 31.18%; E / A > 3.077; E-wave deceleration time < 42.11 and isovolumic relaxation time adjusted by heart rate < 69.08.ConclusionIn rats followed for 6 months after myocardial infarction, the area variation fraction, E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate are predictors of heart failure onset.

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“…[ 11 12 ] Furthermore, SP can decrease collagen synthesis biomarkers in patients with resistant hypertension. [ 13 14 ]…”

Section: Introductionmentioning

confidence: 99%

Fabrication and evaluation of spironolactone-loaded nanostructured lipid carries for cardiac tissue regeneration

et al. 2020

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Mechanisms Involved in the Beneficial Effects of Spironolactone after Myocardial Infarction

Cited by 4 publications

References 32 publications

The role of aldosterone inhibitors in cardiac ischemia–reperfusion injury

The role of aldosterone inhibitors in cardiac ischemia–reperfusion injury

Association between Functional Variables and Heart Failure after Myocardial Infarction in Rats

Fabrication and evaluation of spironolactone-loaded nanostructured lipid carries for cardiac tissue regeneration

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