Dose-dependent effects and mechanisms of exercise-like stimulation on cardiac injury and contractile function: outcomes of the MICRO-ATHLETE study

Luiken, TTJ ORCID: 0000-0002-2312-0414, Cofiño-Fabres, C, Rivera-Arbeláez, JM, Snippert, D, Denessen, EJS, Lamers, SK, Cius, N, van den Dries, K, Mingels, AMA, Thijssen, DHJ ORCID: 0000-0002-7707-5567, Passier, RCJJ and Eijsvogels, TMH (2026) Dose-dependent effects and mechanisms of exercise-like stimulation on cardiac injury and contractile function: outcomes of the MICRO-ATHLETE study. Basic Research in Cardiology. ISSN 0300-8428

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Abstract

Observational studies revealed that exercise produces cardiac troponin release and cardiac fatigue in athletes. However, human in vivo studies offer limited insights into the underlying mechanisms of these potential deleterious effects. This study investigated exercise-induced cardiac troponin release, cardiac fatigue, and its potential mechanisms in a versatile in vitro Engineered Heart Tissue (EHT) model. EHTs were subjected to exercise-like electrical pulse stimulation (EL-EPS) at 2.5 Hz (150 bpm) for 2 or 4 h and compared to non-stimulated controls and doxorubicin (DOX)-exposed tissues. High-sensitive cardiac troponin T (hs-cTnT), lactate dehydrogenase (LDH), and cardiomyocyte contractile function were measured at baseline, immediately after EL-EPS, and after 20 h of recovery. Cell death was quantified by nuclear and mitochondrial DNA concentrations and tissue integrity was assessed using microscopy following exposure. Following 2 and 4 h of EL-EPS, and after DOX exposure, we found increased hs-cTnT and LDH levels and reduced contractile function compared to control. After recovery, contractile function remained impaired after 4 h EL-EPS and DOX exposure, whereas the effects were abolished after recovery for the 2 h EL-EPS group. Elevated nuclear and mitochondrial DNA release was found following DOX, but not after 2 and 4 h EL-EPS. Finally, EL-EPS was associated with the formation of actin aggregates. EL-EPS induced dose-dependent increases in hs-cTnT and LDH concentrations in conjugation with signs of cardiac fatigue, but without elevated markers of permanent cell death (i.e., mitochondrial/nuclear DNA). These findings suggest that exercise-induced elevations of cardiac biomarker concentrations are indicative of reversible cardiac injury.

Item Type:	Article
Uncontrolled Keywords:	Cardiac injury; In vitro exercise; Biomarkers; Cardiac performance; Tissue engineering; Biomarkers; Cardiac injury; Cardiac performance; In vitro exercise; Tissue engineering; 32 Biomedical and Clinical Sciences; 3201 Cardiovascular Medicine and Haematology; Heart Disease; Cardiovascular; Physical Activity; 2.1 Biological and endogenous factors; Cardiovascular; 1102 Cardiorespiratory Medicine and Haematology; Cardiovascular System & Hematology; 3201 Cardiovascular medicine and haematology
Subjects:	R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport and Exercise Sciences
Publisher:	Springer
Date of acceptance:	24 April 2026
Date of first compliant Open Access:	11 June 2026
Date Deposited:	11 Jun 2026 14:39
Last Modified:	11 Jun 2026 14:39
DOI or ID number:	10.1007/s00395-026-01182-9
URI:	https://researchonline.ljmu.ac.uk/id/eprint/28813

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