期刊
ESC HEART FAILURE
卷 8, 期 3, 页码 1806-1818出版社
WILEY PERIODICALS, INC
DOI: 10.1002/ehf2.13308
关键词
Excitation-contraction coupling; Exercise; HFpEF; Metabolic syndrome
资金
- Projekt DEAL
In a metabolic rat model of HFpEF, impaired Ca2+ release was observed under baseline conditions. HIIT and MICT had different effects on Ca2+ homeostasis, with MICT showing positive effects on stroke volume, end-diastolic volume, and cellular arrhythmogenicity.
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 Ca-2(+) 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 Ca-2(+) 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.
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