Effects of different exercise modalities on cardiac dysfunction in heart failure with preserved ejection fraction
Bode, David; Rolim, Natale Pinheiro Lage; Guthof, Tim; Hegemann, Niklas; Wakula, Paulina; Primessnig, Uwe; Berre, Anne Marie Ormbostad; Adams, Volker; Wisløff, Ulrik; Pieske, Burkert; Heinzel, Frank R.; Hohendanner, Felix
Peer reviewed, Journal article
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Date
2021Metadata
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Abstract
Aims
Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent disease. Physical exercise has been shown to alter disease progression in HFpEF. We examined cardiomyocyte Ca2+ homeostasis and left ventricular function in a metabolic HFpEF model in sedentary and trained rats following 8 weeks of moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT).
Methods and results
Left ventricular in vivo function (echocardiography) and cardiomyocyte Ca2+ transients (CaTs) (Fluo-4, confocal) were compared in ZSF-1 obese (metabolic syndrome, HFpEF) and ZSF-1 lean (control) 21- and 28-week-old rats. At 21 weeks, cardiomyocytes from HFpEF rats showed prolonged Ca2+ reuptake in cytosolic and nuclear CaTs and impaired Ca2+ release kinetics in nuclear CaTs. At 28 weeks, HFpEF cardiomyocytes had depressed CaT amplitudes, decreased sarcoplasmic reticulum (SR) Ca2+ content, increased SR Ca2+ leak, and elevated diastolic [Ca2+] following increased pacing rate (5 Hz). In trained HFpEF rats (HIIT or MICT), cardiomyocyte SR Ca2+ leak was significantly reduced. While HIIT had no effects on the CaTs (1–5 Hz), MICT accelerated early Ca2+ release, reduced the amplitude, and prolonged the CaT without increasing diastolic [Ca2+] or cytosolic Ca2+ load at basal or increased pacing rate (1–5 Hz). MICT lowered pro-arrhythmogenic Ca2+ sparks and attenuated Ca2+-wave propagation in cardiomyocytes. MICT was associated with increased stroke volume in HFpEF.
Conclusions
In this metabolic rat model of HFpEF at an advanced stage, Ca2+ release was impaired under baseline conditions. HIIT and MICT differentially affected Ca2+ homeostasis with positive effects of MICT on stroke volume, end-diastolic volume, and cellular arrhythmogenicity.