Lifelong training for improved function of the injured heart

The cardiovascular risk is reduced but not completely diminished by regular physical activity over the lifetime. In addition, exercise-trained people can suffer from myocardial infarction. However, the deleterious effects of a myocardial infarction seem to be reduced by lifelong exercise training, as shown recently in the study of Maessen et al. ¹ As a consequence of myocardial infarction with pathological left-ventricular (LV) remodelling, the LV function is impaired, indicated by reduction of ejection fraction and alteration of wall strain. These deleterious effects are decreased when patients are lifelong physically trained. This indicates that beside other factors such as the severity of the myocardial infarction, clinical treatment (percutaneous coronary intervention), medication use and lifestyle after diagnosis, physical activity over the lifetime is an important factor to protect against harmful effects of myocardial infarction. Although the recent study of Maessen et al. investigated a small group of participants, the result is already worthy of discussion with respect to the mechanisms behind the positive effect and the consequences of this finding for handling patients with myocardial infarction.

The study of Maessen et al. shows that people with higher physical activity remain distinctly active even after the myocardial injury. This could explain the protective effect on the group of patients with physical training, in line with previous animal studies showing the positive effect of physical training on LV remodelling and subsequent LV function. One can speculate that patients with higher physical activity during their lifetime are in a preferable physical condition to perform physical training during the early rehabilitation phase. The higher physical activity after myocardial infarction could induce different mechanisms leading to improved cardiac remodelling. In animal studies, it has been demonstrated that physical training after myocardial infarction can influence different structural and functional factors involved in the myocardial remodelling after infarction.^2,3 The cardiac remodelling process includes preservation and regeneration of ischemic injured myocardium, having a direct effect on terminal differentiated cardiomyocytes, myocardial stem and progenitor cells, and vascular function, as well as structure and modulation of the extracellular matrix (ECM).^4–6 Physical training has been shown to be effective for modification of all these processes. Therefore, cardiac protection could partially be explained by a higher reactivation potential of patients with higher physical activity associated with a preferable physical performance. Another explanation for the observed improvement in LV function and LV remodelling may be physical training during the time before infarction. In animal studies, it has been shown that preconditioning of the heart by physical training before myocardial ischaemia decreases the myocardial injury. The mechanisms behind this could be higher stress protection due to increase of, for example, anti-oxidative enzymes and chaperone proteins, and modulation of calcium homeostasis. ⁷ Although in the case of myocardial infarction these mechanisms cannot be used as protection, they are interesting for all invasive cardiac treatments, which are associated with transient decrease of oxygen supply and potential myocardial damage. A third explanation is the long-term effect of physical activity on the myocardium and vessels. Physical activity influences vessels by long-term improvement of endothelial and vascular function, as well as the structure and regenerative potential of vessels, by inducing endothelial progenitors and increased release of angiogenic factors. ⁸ In the myocardium, cardiac progenitor cells are cellular targets that could be influenced by physical training. The ECM is also an important factor influencing the regeneration of tissue and can be strongly modulated by mechanical and metabolic load induced by physical training. All these processes can be altered if the functional genome is modulated in cell types relevant for myocardial regeneration. It has already been shown that physical activity plays a role in epigenetic modulation of the functional genome in cardiovascular tissue. ⁹

Furthermore, as well as local mechanisms, systemic factors modulated by physical activity over the lifetime, during the period before myocardial infarction and during recovery from infarction could influence the remodelling process. In particular, immune regulation could have a distinct influence on wound healing processes in the myocardium. ¹⁰ Considering the role of physical activity in tuning the immune system, more attention should be directed to this aspect. In addition, it is possible to speculate that several growth factors as well as molecular and cellular carriers, for example microparticles and exosomes, provide signalling from skeletal muscle to injured myocardium, depending on acute and chronic physical activity. ¹¹

At this time, knowledge about the role of physical training in myocardial remodelling after infarction is sparse. Therefore, the study of Maessen et al. demonstrates the value of lifelong physical training, not only for protection against cardiovascular injury, independently of several limitations. Moreover, it provides evidence showing that physical training can also protect the myocardium after injury. In the next steps, it seems that it will be necessary to prove the several possible mechanisms that may lead to the improved LV function after myocardial infarction. This could introduce new prevention and treatment strategies for myocardial infarction.