Key result
Moderate exercise training in mice with severe transverse aortic constriction aggravated heart failure symptoms, increasing heart area by 9% and heart circumference by 7%, while skeletal muscle parameters remained unchanged.
Why the study?
Whether exercise training improves cardiac remodeling and peripheral cachexia in the transverse aortic constriction mouse model had not yet been analyzed.
Does moderate exercise training improve cardiac remodeling and peripheral cachexia in mice with severe TAC-induced heart failure?
RCT (n=45)
Randomized into two groups (exercise vs sedentary)
No
Does moderate exercise training improve cardiac remodeling and peripheral cachexia in mice with severe TAC-induced heart failure?
Moderate exercise training in mice with severe TAC-induced heart failure aggravates cardiac remodeling without improving skeletal muscle function, suggesting this specific model is inappropriate for studying exercise benefits in HF.
Answers are grounded in this paper and cite their sources.
Raises caution for exercise in severe HF models; leaves open suitable protocols or models for benefit studies.
Background Heart failure (HF) is the leading cause of death in western countries. Cardiac dysfunction is accompanied by skeletal alterations resulting in muscle weakness and fatigue. Exercise is an accepted interventional approach correcting cardiac and skeletal dysfunction, thereby improving mortality, re-hospitalization and quality of life. Animal models are used to characterize underpinning mechanisms. Transverse aortic constriction (TAC) results in cardiac pressure overload and finally HF. Whether exercise training improves cardiac remodeling and peripheral cachexia in the TAC mouse model was not analyzed yet. In this study, 2 weeks post TAC animals were randomized into two groups either performing a moderate exercise program (five times per week at 60% VO 2 max for 40 min for a total of 8 weeks) or staying sedentary. Results In both TAC groups HF characteristics reduced ejection fraction (− 15% compared to sham, p < 0.001), cardiac remodeling (+ 22.5% cardiomyocyte cross sectional area compared to sham; p < 0.001) and coronary artery congestion (+ 34% diameter compared to sham; p = 0.008) were observed. Unexpectedly, peripheral cachexia was not detected. Furthermore, compared to sedentary group animals from the exercise group showed aggravated HF symptoms [heart area + 9% (p = 0.026), heart circumference + 7% (p = 0.002), right ventricular wall thickness − 30% (p = 0.003)] while muscle parameters were unchanged [Musculus soleus fiber diameter (p = 0.55), Musculus extensor digitorum longus contraction force (p = 0.90)]. Conclusion The severe TAC model is inappropriate to study moderate exercise effects in HF with respect to cardiac and skeletal muscle improvements. Further, the phenotype induced by different TAC procedures should be well documented and taken into account when planning experiments.
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Böttner et al. (2021) conducted an RCT in Heart failure (induced by severe transverse aortic constriction) (n=45). Moderate exercise training vs. Sedentary was evaluated on Cardiac remodeling and skeletal muscle function. Moderate exercise training in mice with severe transverse aortic constriction aggravated heart failure symptoms, increasing heart area by 9% and heart circumference by 7%, while skeletal muscle parameters remained unchanged.
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