Effects Of Heat Therapy On Skeletal Muscle Interstitial Oxygenation And Mitochondrial Respiration In HFpEF Rats

Heart failure with preserved ejection fraction (HFpEF) impairs skeletal muscle microvascular function and thus physical capacity. Limited options currently exist to treat HFpEF patients. Heat therapy (HT) has demonstrated cardiovascular benefits in health and other diseases, and to enhance nitric oxide (NO) bioavailability and mitochondrial respiration (MR) in health. PURPOSE: To test the hypotheses that chronic HT would 1) elevate skeletal muscle interstitial oxygenation (PO2is) during metabolic transitions thus slowing its fall from rest to contractions (on-kinetics) and accelerating its recovery to baseline (off-kinetics) partly via enhanced NO bioavailability, and 2) improve MR in a rodent model of HFpEF. METHODS: Male obese ZSF1 rats underwent 8 weeks (6 days/wk) of whole-body heat therapy (HT; 39 °C; n = 14) or control (CON; 22 °C; n = 13) interventions. Spinotrapezius (SPI) muscle PO2is was determined via phosphorescence quenching from rest to submaximal contractions and recovery (1 Hz, 4-6 V) under Krebs-Henseleit (KH) and L-NG-Nitro arginine methyl ester (L-NAME). SPI, soleus (SOL), and extensor digitorum longus (EDL) basal (state 2; S2) and maximum (state 3; S3) MR were assessed via high-resolution respirometry (expressed in pmol/s/mg). RESULTS: HT elevated resting SPI PO2is (CON-KH:16.5 ± 1.1, HT-KH:19.5 ± 0.9 mmHg; p < 0.05) and improved (slowed) PO2is on-kinetics partly via enhanced NO bioavailability (T63on; CON-KH:20.9 ± 1.7, CON-L-NAME:19.4 ± 1.5, p > 0.05; HT-KH:26.3 ± 2.1, HT-L-NAME:20.9 ± 1.5 s, p < 0.05). There were no differences in muscle PO2is off-kinetics (T63off, CON-KH:85.8 ± 4.7, HT-KH:88.1 ± 4.7 s, p > 0.05; end-recovery PO2is, CON-KH:13.4 ± 1.6, HT-KH:16.9 ± 1.8 mmHg, p > 0.05). No differences in MR for the SPI (S2, CON:7.5 ± 0.7, HT:7.5 ± 0.6; S3, CON:89.3 ± 6.2, HT:90.8 ± 5.5), SOL (S2, CON:14.5 ± 2.2, HT:17.2 ± 2.0; S3, CON:105.3 ± 22.4, HT:111.9 ± 8.5) or EDL (S2, CON:9.9 ± 2.0, HT:10.7 ± 1.2; S3, CON:128.0 ± 13.6, HT:100.1 ± 7.7) were observed between groups (p > 0.05 for all). CONCLUSION: HT enhanced skeletal muscle PO2is from rest to contractions partly via NO-mediated mechanisms. HT had no effects on skeletal muscle (SPI, SOL or EDL) S2 or S3 MR. These data support that chronic whole-body HT promotes beneficial adaptations within the oxygen transport pathway in a pre-clinical model of HFpEF. ACSM Doctoral Student Research Grant and Purdue University Showalter Grant