Effects of endurance training on detrimental structural, cellular, and functional alterations in skeletal muscles of heart failure with preserved ejection fraction

Background: HFpEF is underpinned by detrimental skeletal muscle alterations that contribute to disease severity, yet underlying mechanisms and therapeutic treatments remain poorly established. This study used an animal model of HFpEF to better understand whether skeletal muscle abnormalities were: 1) fiber-type specific; and 2) reversible by various exercise training regimes.

Methods and Results: Lean controls were compared to obese ZSF1 rats at 20 weeks, and 8 weeks later following sedentary, high-intensity interval training, or moderate-continuous treadmill exercise. Oxidative-soleus and glycolytic-extensor digitorum longus (EDL) muscles were assessed for fiber size, capillarity, glycolytic metabolism, autophagy, and contractile function. HFpEF reduced fiber size and capillarity by 20-50% (P<0.05) in both soleus and EDL, but these effects were not reversed by endurance training. In contrast, both endurance training regimes in HFpEF attenuated the elevated lactate dehydrogenase activity observed in the soleus. Autophagy was downregulated in EDL and upregulated in soleus (P<0.05), with no influence following endurance training. HFpEF impaired contractile forces of both muscles by ∼20 % (P<0.05) and these were not reversed by training.

Conclusion: Obesity-related HFpEF was associated with detrimental structural, cellular, and functional alterations to both slow-oxidative and fast-glycolytic skeletal muscles that could not be reversed by endurance training.