Mesenchymal Stem Cells Increase Resistance Against Ventricular Arrhythmias Provoked in Rats with Myocardial Infarction.

This study evaluated the role of the mesenchymal stem cells derived from adipose tissue (MSCs) in provoked ventricular arrhythmias (VAs) in animals with myocardial infarction (MI). The experimental groups were: sham, subjected to sham surgery and intramyocardial saline injection; MIV, infarcted rats subjected to intramyocardial saline injection; MI + MSCs, infarcted rats subjected to intramyocardial MSCs injection. Injections were performed two days after infarction and the arrhythmogenic inducibility experiment was performed the next day. Only 35% of the MI + MSCs group developed VAs, while the one in the MIV group was 65%. The proportion of nonsustained ventricular tachycardia, sustained tachycardia, and ventricular fibrillation was similar between the infarcted groups, but MSCs animals had shorter duration of nonsustained ventricular tachycardia. However, MSCs increased connexin 43 content in the remote area, even above the levels found in the sham group. MSCs prevented the increase of IL-1ß in the different areas of the myocardium. There was higher carbonylation and content of 4-hydroxynonenal (4-HNE, a marker of lipoperoxidation) in the myocardium of infarcted rats, but MSCs attenuated the increase of 4-HNE in the infarcted area. In conclusion, MSCs have a protective effect against the development of arrhythmias, but do not imply a significant benefit for animals that have developed VAs. It is possible to think that the cardioprotection of MSCs involves anti-inflammatory/oxidative actions and improvement in the formation of communicating junctions.Graphical abstract.

Atrial fibrillation promotion in a rat model of heart failure induced by left ventricle radiofrequency ablation.

BACKGROUND: Atrial fibrillation (AF) frequently coexists with congestive heart failure (CHF). The increased susceptibility to AF in CHF has been attributed to a variety of structural and electrophysiological changes in the atria, particularly dilation and interstitial fibrosis. We evaluated atrial remodeling and AF vulnerability in a rat model of CHF induced by left ventricle (LV) radiofrequency (RF) ablation. METHODS: Wistar rats were divided into 3 groups: RF-induced CHF (Ab, n = 36), CHF animals treated with spironolactone (AbSpi, n = 20) and sham controls (Sham, n = 29). After 12 weeks, animals underwent echocardiographic and electrophysiological evaluation and were sacrificed for histological (atrial fibrosis) and Western blotting (TGF-ß1, collagen I/III, connexin 43 and CaV1.2) analysis. RESULTS: Mild LV dysfunction and marked atrial enlargement were noted in both ablated groups. AF inducibility (episodes ≥2 s) increased in the Ab group compared to sham animals (31/36, 86%; vs. 15/29, 52%; p = 0.005), but did not differ from the AbSpi group (16/20, 80%; p = NS). Sustained AF (>30 s) was also more frequent in the Ab group compared to shams (56% vs. 28%; p = 0.04). Spironolactone reduced atrial fibrosis (p < 0.01) as well as TGF-ß1 (p < 0.01) and collagen I/III (p < 0.01) expression but did not affect connexin 43 and CaV1.2 expression. CONCLUSIONS: Rats with RF-induced CHF exhibit pronounced atrial structural remodeling and enhanced AF vulnerability. This model may be useful for studying AF substrate in CHF.