Effects of heat therapy on exercise tolerance in a rat model of heart failure with preserved ejection fraction.

Abstract

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 wk (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, whereas 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 (Po₂), with and without nitric oxide synthase inhibition (N^G-nitro-l-arginine methyl ester, 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 postintervention (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 Po₂ 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 preclinical model of HFpEF.NEW & NOTEWORTHY This is the first evaluation of the effects of heat therapy (HT) in heart failure with preserved ejection fraction (HFpEF). HT elicited multiple central and peripheral adaptations that impacted positively exercise tolerance in a preclinical model of HFpEF. HT adaptations included improvements in cardiac function, body composition, and skeletal muscle oxygenation (mediated partially via enhanced nitric oxide bioavailability). These novel findings indicate that HT may hold important clinical significance for the treatment of HFpEF.