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

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.