Aerobic exercise training improves left ventricular chamber compliance in Göttingen minipigs

Abstract

Introduction: Exercise training is known to improve left ventricular (LV) function, but the mechanisms remain incompletely understood. Here we investigated the structural and functional adaptations in the LV in response to 2-months of aerobic exercise training in Göttingen minipigs. Methods: Adult male Göttingen minipigs were randomized to an aerobic exercise training regimen of running on a treadmill 3 times per week (N=8, EX) or sedentary housing (N=8, untrained, UT). Structural, functional and molecular measurements were performed in the LV of pigs from both groups at the end of the 2-months period. Results: EX did not affect body weight (35±1 kg vs 37±2 kg EX vs UT) but improved endurance running capacity (75±6 min vs 38±4 min until exhaustion in EX vs UT, P<0.05 by t-test) at the end of the 2-month period, which was associated with enhanced endothelium-dependent vasodilation to bradykinin of small arteries isolated from skeletal small arteries (AUC: 438±46 in EX vs 292±37 in UT, P <0.05 by t-test). EX had no significant effect on LV systolic function (data not shown), but resulted in an increase in LV end-diastolic compliance as the slope of the end-diastolic pressure-volume relationship was lower in EX vs UT ( P<0.05 by 2-way ANOVA). This increase in LV chamber compliance was not due to changes in LV structure as the LV weight to body weight ratio (3.10±0.17 vs 3.15±0.10 g/kg), cardiomyocyte cross-sectional area (100±10 vs 104±8 mm2) and collagen content (7.6±0.3 vs 6.6±0.4% myocardium area) were not significantly different between UT and EX. In contrast, single LV cardiomyocyte stiffness was reduced in EX compared to UT ( P<0.05 by 2-way ANOVA), likely caused by a shift in titin isoform towards the more compliant N2BA isoform (N2BA/N2B ratio: 1.22±0.03 vs 0.95±0.05; P<0.05 by t-test). Conclusion: Two months of aerobic exercise training 3 times per week increased LV diastolic chamber compliance, which was mediated, at least in part, through a titin isoform shift and a decreased myocyte stiffness, in the absence of LV structural changes. Dutch CardioVascular Alliance: An initiative with support of the Dutch Heart Foundation (Grants 2017B018 ARENA-PRIME and 2020B008 RECONNEXT) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.