Arrhythmogenic right ventricular (RV) remodeling has been reported in response to regular training, but it remains unclear how exercise intensity affects the presence and extent of such remodeling. We aimed to assess the relationship between RV remodeling and exercise load in a long-term endurance training model. Wistar rats were conditioned to run at moderate (MOD; 45 min, 30 cm/s) or intense (INT; 60 min, 60 cm/s) workloads for 16 wk; sedentary rats served as controls. Cardiac remodeling was assessed with standard echocardiographic and tissue Doppler techniques, sensor-tip pressure catheters, and pressure-volume loop analyses. After MOD training, both ventricles similarly dilated (~16%); the RV apical segment deformation, but not the basal segment deformation, was increased [apical strain rate (SR): −2.9 ± 0.5 vs. −3.3 ± 0.6 s−1, SED vs. MOD]. INT training prompted marked RV dilatation (~26%) but did not further dilate the left ventricle (LV). A reduction in both RV segments' deformation in INT rats (apical SR: −3.3 ± 0.6 vs. −3.0 ± 0.4 s−1 and basal SR: −3.3 ± 0.7 vs. −2.7 ± 0.6 s−1, MOD vs. INT) led to decreased global contractile function (maximal rate of rise of LV pressure: 2.53 ± 0.15 vs. 2.17 ± 0.116 mmHg/ms, MOD vs. INT). Echocardiography and hemodynamics consistently pointed to impaired RV diastolic function in INT rats. LV systolic and diastolic functions remained unchanged in all groups. In conclusion, we showed a biphasic, unbalanced RV remodeling response with increasing doses of exercise: physiological adaptation after MOD training turns adverse with INT training, involving disproportionate RV dilatation, decreased contractility, and impaired diastolic function. Our findings support the existence of an exercise load threshold beyond which cardiac remodeling becomes maladaptive.

Support for this work was partially funded by Generalitat de Catalunya Grants FI-AGAUR 2014-2017 and RH040991 (to M. Sitges), the Spanish government (Plan Nacional I + D, Ministerio de Economia y Competitividad Grants DEP2010-20565, DEP2013-44923-P, and TIN2014-52923-R, cofinanced by the Fondo Europeo de Desarrollo Regional de la Unión Europea “Una manera de hacer Europa”), Instituto de Salud Carlos III Grants PI13/01580 and PI16/00703, and Centro de Investigación BIomédica en Red-Cardiovascular CB16/11/00354.