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 the effects of 1- to 2-wk swim training on cardiac and systemic phenotype in young male C57Bl/6 mice. Two-week forced swimming (90 min twice daily) resulted in cardiac hypertrophy (22% increase in heart:body weight, <i>P</i> < 0.01), with improved inotropy (22% higher left ventricular +dP/d<i>t</i>, <i>P</i> < 0.01) and functional tolerance to ischemia-reperfusion (I-R) (40%-50% reductions in stunning and diastolic dysfunction, <i>P</i> < 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, and OPA-1), or stress signaling (caveolin-3 and GSK-3β). Furthermore, no changes in cardiac cytokines (IL-1b, IL-6, IL-10, IL-12, GM-CSF, TNF-α, and 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, and EphB4), together with a fall in M-CSF R and ephrin sub-type receptor phosphorylation. Swimming increased growth factor while reducing inflammatory mediators across extracardiac tissues [brain, pancreas, thymus, lymph nodes, and white adipose tissue (WAT)]. This included a pattern of increased LIF, VEGF, and pentraxin-2 versus 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. In summary, 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.<b>NEW & NOTEWORTHY</b> Swimming may induce cardiac and systemic benefits distinct from other modes of physical activity. We show that 2-wk forced swim training increases cardiac growth, contractility, and functional resilience to ischemia in hearts of male mice. This is associated with increased growth factor levels and reduced inflammatory and lipogenic protein profiles in peripheral tissues.