Cardiac Protection from Ischemia-Reperfusion Injury in Swimming Mice

PURPOSE:The purpose of this study was to determine whether cardiac protection from ischemia could be afforded with a forced-swimming as a higher intensity and stress model of exercise. We hypothesised was that higher-intensity training via forced swimming might invoke additional protective mechanisms or pathways than those previously reported in response to lower intensity voluntary activity such as wheel running. METHODS: Male C57Bl/6 mice swam for 90 min twice a day for 1 or 2 wk before randomly assigned to either 1) molecular analysis of cardiac pro-survival kinases with Phospho-Receptor Tyrosine Kinase (P-RTK) Proteome arrays and Western Immunoblotting, 2) transcriptional adaptations via qRT-PCR, or 3) global ischemia-reperfusion injury assessment via Langendorff isolated heart preparation with 25-min ischemia/45-min reperfusion. RESULTS: Hearts exhibited physiological hypertrophy (15.44% and 22% increase in Heart:Body weight ratio compared to sedentary controls in 1 and 2 wk groups respectively). Langendorff perfusion revealed left ventricular developed pressure (LVDP) improved (61.46% ± 5.7 vs. 44.35% ± 3.7, P<0.01) and end diastolic pressure was reduced (EDP mmHg: 12.68 ± 1.8 vs. 27.40 ± 1.8, P<0.01) following 2 wks of swim training. Subsequent gene and protein expression showed differential signaling in pro-survival kinases and other cardioprotective mechanisms. Pooled sample proteome arrays within the 2-week group showed exercised mice exhibited greater phosphorylation of various growth factors such as Insulin receptor, IGF-1R, FGF, HGF, PDGF. Protein expression of NFKB was reduced in exercised groups. CONCLUSIONS: These data indicate that swimming mice exhibited significant cardioprotection compared to the sedentary group after 2 weeks of exercise. Subsequent proteomic screening showed that in the 2-week group, a number of P-RTK growth factor receptors were activated in response to exercise. The anti-inflammatory and activation of pro-survival kinases due to the hormetic effect of exercise warrants further investigation.