Impact Of High-intensity Interval Training On Cardiac Morphology Assessed By MRI In Postnatal Growth-restricted Mice

Postnatal growth-restriction (PNGR) leads to lasting deficits in growth and heart health, increasing the risk of cardiovascular disease in adulthood by 47%. Adverse cardiac changes, including fibrosis, have been reported in PNGR mice following voluntary wheel running. However, high-intensity interval training (HIIT) is proposed as a more effective option compared to voluntary wheel running and moderate-intensity continuous exercise, improving vascular function and cardiac morphology by providing a stronger and more efficient physiological stimulus. While echocardiography relies on geometrical assumptions, MRI provides precise 3D imaging for accurate assessment of heart structure and function, enabling a more accurate and detailed analysis of how HIIT affects cardiac outcomes. PURPOSE: This study investigated whether HIIT can improve cardiac function in PNGR mice, using MRI for comprehensive structural and functional analysis. METHODS: FVB mice from normal- or low-protein fed dams were cross-fostered on postnatal day (PN) 1, assigned into PNGR or control (CON) groups, and weaned onto a normal diet at PN 21. They were assigned to HIIT or sedentary groups. At PN 45, a maximal exercise performance test was conducted to set HIIT intensities. Based on the maximal exercise performance test, mice performed 60-minute HIIT sessions, 5 days a week, for 4 weeks. At PN 73, cardiac MRI was conducted. RESULTS: PNGR mice (1.21 ± 0.031 J/min) had lower baseline exercise capacity compared to CON mice (1.44 ± 0.031 J/min, P < 0.0001). HIIT significantly increased work capacity across groups, including CON males, PNGR males, and PNGR females (P < 0.0001). MRI showed that cardiac output was significantly reduced in PNGR mice (11.50 ± 2.51 ml) compared to CON mice (13.56 ± 1.57 ml, P = 0.0010). Similarly, the stroke volume index was lower in PNGR mice (0.37 ± 0.07 μl/cm2) compared to CON mice (0.42 ± 0.06 μl/cm2, P = 0.0245). PNGR mice had thinner left ventricle walls during systole (1.31 ± 0.21 mm) compared to CON mice (1.46 ± 0.18 mm, P = 0.0414) and exhibited smaller wall thickness differences (0.27 ± 0.09 mm) compared to CON (0.44 ± 0.12 mm, P = 0.0001). CONCLUSION: HIIT improved exercise capacity in PNGR mice but did not significantly enhance cardiac structure or function compared to CON, indicating limited cardiovascular benefits.