Aerobic interval training preconditioning protocols inhibit isoproterenol-induced pathological cardiac remodeling in rats: Implications on oxidative balance, autophagy, and apoptosis

Abstract

This study aimed to investigate the potential cardioprotective effects of moderate and high-intensity aerobic interval training (MIIT and HIIT) preconditioning. The focus was on histological changes, pro-oxidant-antioxidant balance, autophagy initiation, and apoptosis in myocardial tissue incited by isoproterenol-induced pathological cardiac remodeling (ISO-induced PCR). Male Wistar rats were randomly divided into control (n ​= ​6), ISO (n ​= ​8), MIIT (n ​= ​4), HIIT (n ​= ​4), MIIT ​+ ​ISO (n ​= ​8), and HIIT ​+ ​ISO (n ​= ​8) groups. The MIIT and HIIT protocols were administered for 10 weeks, followed by the induction of cardiac remodeling using subcutaneous injection of ISO (100 ​mg/kg for two consecutive days). Alterations in heart rate (HR), mean arterial pressure (MAP), rate pressure product (RPP), myocardial oxygen consumption (MV˙O₂), cardiac hypertrophy, histopathological changes, pro-oxidant-antioxidant balance, autophagy biomarkers (Beclin-1, Atg7, p62, LC3 I/II), and apoptotic cell distribution were measured. The findings revealed that the MIIT ​+ ​ISO and HIIT ​+ ​ISO groups demonstrated diminished myocardial damage, hemorrhage, immune cell infiltration, edema, necrosis, and apoptosis compared to ISO-induced rats. MIIT and HIIT preconditioning mitigated HR, enhanced MAP, and preserved MV˙O₂ and RPP. The pro-oxidant-antioxidant balance was sustained in both MIIT ​+ ​ISO and HIIT ​+ ​ISO groups, with MIIT primarily inhibiting pro-apoptotic autophagy progression through maintaining pro-oxidant-antioxidant balance, and HIIT promoting pro-survival autophagy. The results demonstrated the beneficial effects of both MIIT and HIIT as AITs preconditioning in ameliorating ISO-induced PCR by improving exercise capacity, hemodynamic parameters, and histopathological changes. Some of these protective effects can be attributed to the modulation of cardiac apoptosis, autophagy, and oxidative stress.

Keywords

Pathological cardiac remodeling / Aerobic interval training preconditioning / Oxidative stress / Autophagy / Apoptosis

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The present manuscript is derived from a Ph.D. thesis (NO: 11112). The authors wish to extend their gratitude for the scientific support received from the Faculty of Sport Sciences, Urmia University, and the School of Pharmacy, Urmia University of Medical Sciences. Furthermore, the authors would like to acknowledge the valuable assistance provided by the RASTA special research institute (RSRI) in the laboratory.