Effects of Heat Therapy on Exercise Tolerance in a Rat Model of Heart Failure with Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) impairs cardiac and skeletal muscle function, reducing exercise tolerance. Few therapies are available to improve physical capacity in HFpEF. We tested the hypothesis that chronic whole-body heat therapy (HT) induces central and peripheral adaptations that enhance exercise tolerance in a model of HFpEF. Male obese ZSF1 rats underwent 8 weeks (6 days/wk) of HT (n=14) or control (CON; n=13) interventions. HT was delivered by placing animals in chambers set to 39°C, while CON animals were placed in chambers kept at room temperature (~22°C). Assessments included exercise tolerance, body composition, echocardiography, mitochondrial respiration, and skeletal muscle interstitial oxygenation (PO 2 ), with and without nitric oxide synthase inhibition (L-NAME). HT prevented the decline in exercise tolerance (PRE:411±13, POST:427±11; p>0.05) observed in CON (PRE:441±16, POST:344±17 s; p<0.05). Similarly, HT preserved left ventricular ejection fraction (PRE:71.5±1.3, POST:74.1±1.6; p>0.05), which declined in CON (PRE:72.2±2.0, POST:67.4±2.2 %; p<0.05). Total body mass was not different between groups post-intervention (CON:624±12, HT:617±14 g; p>0.05). CON increased fat mass (PRE:0.37±0.01, POST:0.38±0.01; p<0.05) without affecting lean mass (PRE:0.56±0.01, POST:0.56±0.01; p>0.05). In contrast, HT reduced fat mass (PRE:0.38±0.01, POST:0.34±0.01; p<0.05) and increased lean mass (PRE:0.56±0.01, POST:0.61±0.01; p<0.05). HT improved resting and contracting muscle PO 2 partly via enhanced nitric oxide bioavailability. There were no differences in skeletal muscle mitochondrial respiration between groups. These findings indicate that HT promotes central and peripheral adaptations that improve exercise tolerance in a pre-clinical model of HFpEF.