Swimming induces physiological cardioprotection associated with pro-growth versus anti-inflammatory influences in extracardiac organs

Physical activity improves myocardial structure, function and resilience via complex, incompletely defined mechanisms. We explored effects of 1-2 wks swim training on cardiac and systemic phenotype in young male C57Bl/6 mice. Two wks forced swimming (90 min twice daily) resulted in cardiac hypertrophy (22% increase in heart:body weight, P<0.01), with improved inotropy (22% higher left ventricular +dP/dt, P<0.01) and functional tolerance to ischemia-reperfusion (I-R) (40-50% reductions in stunning and diastolic dysfunction, P<0.01; without changes in cell death assessed from enzyme loss) in Langendorff perfused hearts. Initial Western immunoblot analysis indicated no shifts in cardiac expression of determinants of autophagy (LC3A/B), mitochondrial biogenesis/dynamics (PGC-1α, MFN-1, OPA-1) or stress signaling (caveolin-3, GSK-3β). Furthermore, no changes in cardiac cytokines (Il-1b, Il-6, Il-10, Il-12, GM-CSF, TNF-α, IFN-γ) were detected in multiplex immunoassays. Exploratory profiling of RTK phosphorylation provided evidence for moderately increased activity of receptors involved in cardiac/coronary growth and protection (insulin, IGF-1, FGF R2, Tie-2, PDGFβ, EphB4), together with a fall in M-CSF R and ephrin sub-type receptor phosphorylation. Swimming increased growth factor while reducing inflammatory mediators across extra-cardiac tissues (brain, pancreas, thymus, lymph nodes, white adipose tissue - WAT). This included a pattern of increased LIF, VEGF and pentraxin-2 vs. reduced CXCL2/MIP-2a, chitinase 3-like 1, CCL6, MMP9, CD40/TNFRSF5 and IGFBP6 in multiple tissues; and a shift to a pro-browning profile in WAT. Summarizing: swimming produces integrated systemic benefits, improving cardiac growth, inotropy and resilience in association with increased growth factor and reduced inflammatory and lipogenic mediators in multiple tissues.