Clin Res Cardiol (2022).

Exercise training during cardiac pressure overload in rats with high or low intrinsic exercise capacity
C. Schenkl1, M. Schwarzer1, M. Kravchenko1, M. Schwarz1, L. Koch2, S. L. Britton3, T. Doenst1
1Klinik für Herz- und Thoraxchirurgie, Universitätsklinikum Jena, Jena; 2Department of Physiology and Pharmacology, University of Toledo, Toledo, US; 3Department of Anesthesiology, University of Michigan, Ann Arbor, US;

Objectives Exercise capacity of an individual consists of an intrinsic (genetically determined) and an extrinsic (acquired) part. Low exercise capacity is a risk factor for cardiovascular diseases and associated with shortened lifespan. In contrast, high exercise capacity and improving it by exercise training is considered beneficial. We assessed the role of exercise capacity and exercise training during cardiac pressure overload (PO) in a rat model for high (HCR) or low (LCR) intrinsic exercise capacity.

Methods Pressure overload was induced in HCR and LCR rat weanlings by transverse aortic constriction (TAC). We performed echocardiography regularly, documented survival time and measured cardiac mitochondrial respiratory capacity (State 3) using a Clark-type electrode. Exercise training (5 d/week) was performed on a treadmill as high intensity aerobic exercise individualized to the rats’ own exercise capacity.

Results With pressure overload, mean survival time of LCR exceeded HCR’s by 23% (p=0.026). Ratios of heart- and lung-to-body weight increased in both phenotypes (LBI: HCR-TAC +82% and LCR-TAC +83%) indicating cardiac hypertrophy and lung congestion. Only HCR showed structural changes of lung tissue. Echocardiography revealed stronger impairment of diastolic function in HCR compared to LCR (E/A: HCR-TAC 3,16±0,48 vs. LCR-TAC 1,80±0,15) after two weeks of PO. In parallel, ejection fraction was also more reduced in HCR compared to LCR after 10 weeks of pressure overload (EF: HCR-TAC 61,13±3,20% vs. LCR-TAC 76,02±3,60%). Cardiac mitochondrial function was not different between HCR and LCR.

Exercise training during pressure overload improved running capacity (distance and VO2max) in LCR but actually lowered exercise capacity in HCR (VO2max: LCR-TAC +18% and HCR-TAC -15%). Exercise increased mortality in both groups but delayed the onset of diastolic dysfunction in LCR and systolic dysfunction in survivors of both phenotypes. Mitochondrial state 3 respiration decreased in exercised rats with PO, which was more pronounced in HCR (-28%) than LCR (-8%).

Conclusion Contrary to expectations, pressure overload in rats with high intrinsic exercise capacity caused more death and severe cardiac dysfunction than in rats with low intrinsic exercise capacity. There was no protective impact of additional exercise in rats subjected to pressure overload.