Exercise training reduces ventricular arrhythmias through restoring calcium handling and sympathetic tone in myocardial infarction mice

Abstract

Exercise can improve morbidity and mortality in heart failure patients; however, the underlying mechanisms remain to be fully investigated. Thus, we investigated the effects of exercise on cardiac function and ventricular arrhythmias in myocardial infarction (MI) induced heart failure mice. Wild‐type male mice underwent sham‐operation or permanent left coronary artery ligation to induce MI. MI mice were divided into a sedentary (MI‐Sed) and two intervention groups: MI‐Ex (underwent 6‐week treadmill exercise training) and MI‐βb (oral bisoprolol treatment (1 mg/kg/d) without exercise). Cardiac function and structure were assessed by echocardiography and histology. Exercise capacity and cardiopulmonary function was accepted as oxygen consumption at peak exercise (peak VO 2 ). Autonomic nervous system function and the incidence of spontaneous ventricular arrhythmia were evaluated via telemetry recording. mRNA and protein expressions in the left ventricle (LV) were investigated by real‐time PCR and Western blotting. There were no differences in survival rate, MI size, cardiac function and structure, while exercise training improved peak VO 2 . Compared with MI‐Sed, MI‐Ex, and MI‐βb showed decreased sympathetic tone and lower incidence of spontaneous ventricular arrhythmia. By Western blot, the hyperphosphorylation of CaMKII and RyR2 were restored by exercise and β‐blocker treatment. Furthermore, elevated expression of miR‐1 and decreased expression of its target protein PP2A were recovered by exercise and β‐blocker treatment. Continuous intensive exercise training can suppress ventricular arrhythmias in subacute to chronic phase of MI through restoring autonomic imbalance and impaired calcium handling, similarly to that for β‐blockers.

The oxidation‐resistant CaMKII‐MM281/282VV mutation does not prevent arrhythmias in CPVT1

“…We can only speculate why the CPVT1 mice (Manotheepan et al, 2016). One such mechanism might depend on protein phosphatase 2A, shown to be upregulated in exercise (Qin et al, 2019), which can dephosphorylate RyR2-S2814 (Terentyev & Hamilton, 2016), and might have contributed to the decreased phosphorylation found in RyR2-RS following exercise.…”

Nicotinamide Phosphoribosyltransferase (Nampt)/Nicotinamide Adenine Dinucleotide (NAD) Axis Suppresses Atrial Fibrillation by Modulating the Calcium Handling Pathway

“…Finally, we used NR, a pyridine-nucleoside form of vitamin B that functions as a NAD precursor [40], to assess whether NR can recover the negative effects arising from NKO. NR has been proven to effectively increase NAD synthesis in various tissues and organs such as the heart, skeletal muscle, adipose tissue, and liver [19,29,41,42].…”

“…Echocardiography was conducted as described previously [40,46]. At 5 and 13 weeks of age, parasternal long-axis and short-axis views were obtained at the papillary muscle level under anesthesia with isoflurane using an echocardiographic system (Vevo 2100; Visual Sonics, Toronto, Canada).…”

“…Western blotting was performed as described previously [40,45]. Briefly, isolated atrial tissues were homogenized in PRO-PREP protein extraction solution (iNtRON Biotechnology Inc. Kyungki-Do, Korea), and the supernatants were used for western immunoblotting.…”

Efeitos do Exercício Aeróbico Tardio na Remodelação Cardíaca de Ratos com Infarto do Miocárdio Pequeno

“…6 O exercício aeróbico tem sido o foco de muitos estudos sobre a atenuação da remodelação cardíaca induzida por IM, melhora da capacidade funcional e qualidade de vida. [7][8][9][10] Modelos animais de IM são amplamente usados para estudar a fisiopatologia e o tratamento da remodelação cardíaca. A maioria dos estudos que avaliam os efeitos do exercício nas alterações cardíacas pós-infarto do miocárdio utilizou roedores com grandes áreas de infarto, geralmente mais de 30% da área total do ventrículo esquerdo (VE).…”