Structural and functional alterations in heart and skeletal muscle following severe TAC in mice: impact of moderate exercise training

Abstract

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% VO2 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.

Cryogenic contrast-enhanced microCT enables nondestructive 3D quantitative histopathology of soft biological tissues

“…For instance, a common practice to determine the cardiac muscle fiber diameter is to measure the cross-sectional area (CSA) of the fibers, based on classical 2D histological sections. However, the CSA highly depends on the sectioning orientation and location and, therefore, leads to a wide range of reported fiber diameters for wild-type mice (8 − 22 µm) [75][76][77] . In addition, the sample dehydration step required for classical 2D histological sectioning causes substantial tissue shrinkage, which can result in an erroneous quantification of the fiber diameter (Supplementary Fig.…”