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Limb Blood Flow Restriction Plus Mild Aerobic Exercise Training Protects the Heart Against Isoproterenol-Induced Cardiac Injury in Old Rats: Role of GSK-3β

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Abstract

The present study was conducted to evaluate the effect of blood flow restriction (BFR) training on cardiac resistance to isoproterenol (ISO) induced heart injury in old rats and examined the hypothesis that BFR training may interfere with age-associated impairment of mitochondria by the inhibitory phosphorylation of GSK-3β at Ser9. Old male Wistar rats were divided into the following six groups: CTL (control), ISO (isoproterenol-treated), Sh + ISO (sham-operated plus ISO), BFR + ISO (blood flow restriction plus ISO), Sh-Ex + ISO (sham-operated subjected to exercise and ISO), and BFR-Ex + ISO (blood flow restriction along with exercise and ISO). 10 weeks of exercise training was considered. Then, cardiac injury was induced and physiological, histological, and biochemical parameters were recorded and assessed. Compared to CTL group, isoproterenol administration significantly reduced the systolic arterial pressure (SAP), left-ventricular systolic pressure (LVSP), and ± dp/dt max (P < 0.05). BFR training improved these parameters in the way that BFR-Ex + ISO group had higher SAP, LVSP and ± dp/dt max (P < 0.05) and lower LVEDP (left-ventricular end diastolic pressure) (P < 0.01) than untrained and Sh-Ex + ISO groups. The pS9-GSK-3β and pS9-GSK-3β/GSK-3β ratio were increased in the BFR-Ex + ISO group compared to CTL, ISO, Sh + ISO, and BFR + ISO groups (P < 0.05). The level of plasma cardiac Troponin-I and the severity of the injuries were significantly reduced in BFR-Ex + ISO group versus other cardiac damaged groups. In conclusion, our findings clearly confirmed the cardio-protective effect of BFR training against ISO-induced myocardial injury. Increased phosphorylated GSK-3β and angiogenesis in this model of exercise justify the resistance of old hearts facing stressful situations.

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Acknowledgements

The authors are thankful to Dr. Behzad Behbahani and Mrs. Samaneh Naderi from Diagnostic Laboratory Science and Technology Research Center, Shiraz, Iran, for their technical supporting and providing laboratory equipment. We are also grateful to Miss Elham Nadimi for her help and encouragement in histological evaluations. This work was financially supported by Kerman University of Medical Sciences, Kerman, Iran, (1394/495) and provided from the results of PhD thesis of Mrs. V. Naderi-boldaji.

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Authors and Affiliations

  1. Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Department of Physiology and Pharmacology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

    Vida Naderi-Boldaji

  2. Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Department of Physiology and Pharmacology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, P. O. Box 7616914115, Kerman, Iran

    Siyavash Joukar

  3. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Vida Naderi-Boldaji & Siyavash Joukar

  4. Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Ali Noorafshan

  5. Department of Physical Education, Faculty of Shahid Chamran, Kerman Branch, Technical and Vocational University (YVU), Tehran, Iran

    Mohammad-Ali Bahreinipour

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  1. Vida Naderi-Boldaji
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Correspondence to Siyavash Joukar.

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Ethical Approval

All applicable national guidelines for the care and use of animals were followed. The study was approved by the Ethical Committee in Research of the Kerman University of medical science, Kerman, Iran (permission No IR.KMU.REC.1394.495) and the experimental protocol was conducted in accordance with the guidelines of that university for conducting animal studies.

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Naderi-Boldaji, V., Joukar, S., Noorafshan, A. et al. Limb Blood Flow Restriction Plus Mild Aerobic Exercise Training Protects the Heart Against Isoproterenol-Induced Cardiac Injury in Old Rats: Role of GSK-3β. Cardiovasc Toxicol 19, 210–219 (2019). https://doi.org/10.1007/s12012-018-9490-y

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