Effects of heat therapy on skeletal muscle interstitial oxygenation and exercise tolerance in HFpEF rats

Heart failure with preserved ejection fraction (HFpEF) impairs skeletal muscle microvascular function and blood flow thereby reducing exercise tolerance. Limited therapies currently exist to restore physical capacity in HFpEF. Heat therapy has been shown to improve cardiovascular outcomes and exercise tolerance in health and other diseases. PURPOSE: To test the hypothesis that chronic whole-body heat therapy would improve heart function and morphology, body composition, skeletal muscle interstitial oxygenation (PO2) and, therefore, exercise tolerance in a rodent model of HFpEF. METHODS: Male obese ZSF1 rats (5-6 mo) underwent either 8 weeks (6 days/wk) of heat therapy (HT; 39°C; n=10) or control (CON; 22°C; n=8) interventions. Exercise tolerance (treadmill tests to exhaustion), body composition (echoMRI) and heart function and morphology (echocardiography) were assessed pre- and post-intervention. Spinotrapezius PO2 (phosphorescence quenching) was assessed post-intervention from rest to submaximal contractions (1 Hz, 5-7 V, 3 min). RESULTS: Repeated HT prevented the decline in the main outcome of exercise tolerance (PRE:424±17, POST:425±13 s; p>0.05) observed in CON (PRE:444±24, POST:319±24 s; p<0.05). Left ventricular mass was not different between groups over the study period (CON PRE:2.5±0.1, POST:2.6±0.1; HT PRE:2.4±0.1, POST:2.3±0.2 mg/g; p>0.05). There were no differences in isovolumetric relaxation time after treatment (CON PRE:23±2, POST:24±1; HT PRE:21±1, POST:24±2 ms; p>0.05). HT averted the decline in left ventricular ejection fraction (PRE:71.3±1.7, POST:73.7±2.3 %; p>0.05) observed in CON (PRE:75.3±0.9, POST:67.9±4.0 %; p<0.05). Total body mass increased in both groups during the 8 wk intervention period (CON PRE:564±8, POST:647±12; HT PRE:550±17, POST:631±18 g; p<0.05). While total fat mass (normalized to body mass) was not different after CON (PRE:0.37±0.01, POST:0.38±0.01 g/mg; p>0.05), it was reduced after HT (PRE:0.38±0.01; POST:0.35±0.01 g/mg; p<0.05). Similarly, total lean mass was not different after CON (PRE:0.56±0.01, POST:0.56±0.01 g/mg; p>0.05) but was increased after HT (PRE:0.56±0.01, POST:0.60±0.01 g/mg; p<0.05). In addition, HT elevated the resting spinotrapezius PO2 (CON:15.9±1.4, HT:19.1±1.0 mmHg; p<0.05) and improved (slowed) the overall speed of PO2 fall during muscle contractions (T63; CON:18±2, HT:23±1 s; p<0.05). CONCLUSIONS: Repeated HT preserves left ventricular ejection fraction and exercise tolerance whilst improving body composition in rats with HFpEF. Moreover, HT enhances skeletal muscle interstitial PO2 from rest to submaximal contractions. Chronic whole-body HT promotes central and peripheral adaptations that impact positively exercise tolerance in a pre-clinical model of HFpEF. ACSM Doctoral Student Research Grant and Purdue University. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.