A Comparative Study: Cardioprotective Effects of High-Intensity Interval Training Versus Ischaemic Preconditioning in Rat Myocardial Ischaemia-Reperfusion

Abstract

(1) Background: Years of research have identified ischemic preconditioning (IPC) as a crucial endogenous protective mechanism against myocardial ischemia-reperfusion injury, enhancing the myocardial cell's tolerance to subsequent ischemic damage. High-intensity interval training (HIIT) is promoted by athletes because it reduces exercise duration and improves metabolic response and cardiopulmonary function. Our objective was to evaluate and compare whether HIIT and IPC could reduce myocardial ischemia and reperfusion injury in rats. (2) Methods: Male Sprague-Dawley rats were divided into four groups: sham surgery, coronary artery occlusion (CAO), high-intensity interval training (HIIT), and ischemic preconditioning (IPC). The CAO, HIIT, and IPC groups experienced 40 min of coronary artery occlusion followed by 3 h of reperfusion to induce myocardial ischemia-reperfusion injury. Subsequently, the rats were sacrificed, and blood samples along with cardiac tissues were examined. The HIIT group received 4 weeks of training before surgery, and the IPC group underwent preconditioning before the ischemia-reperfusion procedure. (3) Results: The HIIT and IPC interventions significantly reduced the extent of the myocardial infarction size and the levels of serum troponin I and lactate dehydrogenase. Through these two interventions, serum pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, were significantly decreased, while the anti-inflammatory cytokine IL-10 was increased. Furthermore, the expression of pro-apoptotic proteins PTEN, caspase-3, TNF-α, and Bax in the myocardium was reduced, and the expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) was increased, ultimately reducing cellular apoptosis in the myocardium. In conclusion, both HIIT and IPC demonstrated effective strategies with potential for mitigating myocardial ischemia-reperfusion injury for the heart.

Keywords: apoptosis; coronary artery occlusion; high-intensity interval training; ischemic preconditioning; myocardial ischemia and reperfusion injury.

Figure 1

Study design of the experiment. All rats except for those in the sham group underwent a 40 min coronary artery occlusion and 3 h reperfusion after receiving various treatments. The sham group did not receive any pretreatment during the treatment period. Before the experiment, the HIIT group underwent 4 weeks of high-intensity interval training. The IPC group underwent ischemic preconditioning through two 10 min episodes of coronary artery occlusion and 10 min reperfusion. HIIT, high–intensity interval training; IPC, ischemic preconditioning.

Figure 2

(A) Area at risk for ischemia (AAR; Evans blue staining) and infarct area (IFA; 1% 2,3,5-triphenyl-2H-tetrazolium chloride (TTC)) in representative heart sections from the CAO, HIIT, and IPC groups. (B) Size of AAR, expressed as a percentage of LV. (C) Size of MI, expressed as a percentage of AAR. * p < 0.001 vs. CAO group (n = 6). AAR = area at risk; LV = left ventricle; MI = myocardial infarct.

Figure 3

Biochemical analysis of cardiac function. (A) Troponin I level. (B) Lactate dehydrogenase (LDH) level. *, p < 0.001 vs. sham group; &, p < 0.01 vs. CAO group; #, p < 0.001 vs. CAO group (n = 6). CAO, coronary artery occlusion; LDH, lactate dehydrogenase.

Figure 4

Histological examination of cardiac injury. (A) Representative photomicrographs of heart sections stained with hematoxylin and eosin (400× magnification). Normal morphology of the rats’ myocardial tissue in the sham group. Interstitial swelling, myocardial cell edema, and myocardial fibers disruption in the CAO group. (B) Histological injury scoring of the myocardial tissue. *, p < 0.001 vs. sham group; #, p < 0.001 vs. CAO group (n = 4). CAO, coronary artery occlusion.

Figure 5

Cardiac apoptosis analysis. (A) Illustrative photomicrographs of TUNEL staining (400× magnification). TUNEL-positive nuclei are stained in dark brown and indicated with red arrow. (B) The percentage of TUNEL-positive nuclei. *, p < 0.001 vs. sham group; #, p < 0.001 vs. CAO group (n = 4). TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling.

Figure 6

Serum levels of (A) tumor necrosis factor-α (TNF-α), (B) interleukin-1β, (C) interleukin-6, (D) interleukin-10. *, p < 0.001 vs. sham group; #, p < 0.001 vs. CAO group. Blood samples were collected from six rats in each group to determine the serum levels of TNF-α, interleukin-1β, interleukin-6, and interleukin-10 (n = 6). TNF-α, tumor necrosis factor-α.

Figure 7

Evaluation of (A) PTEN, (B) Bax-to-Bcl-2 ratio, (C) TNF-α, and (D) cleaved-caspase-3-to-proactive-caspase-3 ratio. Illustrative Western blots of PTEN, Bax-to-Bc-2 ratio, TNF-α, cleaved-aspase-3-to-proactive-caspase-3 ratio (upper). The density of PTEN, Bax-to-Bc-2 ratio, TNF-α level, cleaved-caspase-3-to-proactive-caspase-3 ratio were analyzed using arbitrary units (lower). *, p < 0.001 vs. sham group; $, p < 0.05 vs. sham group; #, p < 0.001 vs. CAO group CAO, coronary artery occlusion; TNF-α, tumor necrosis factor-α.