Time to Exercise: Circadian Regulation of Cardiac Preconditioning
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Myocardial ischemia reperfusion injury remains a significant health concern worldwide. The pursuit of therapeutic interventions to reduce the severity of ischemia reperfusion (IR) injury by preconditioning the heart has been ongoing for decades, and through preclinical studies the approach broadly includes three methodological categories; ischemic, pharmacological, and exercise preconditioning. These efforts have yielded many exciting experimental candidates, which have largely been unsuccessfully translated into clinical practice. One potential hurdle in clinical translation and efficacy of myocardial preconditioning may involve the circadian rhythm (i.e. – the ~24 hour recurring cycles in physiological processes), and the experimental or clinical timing of interventions designed to improve cardiac outcomes. Circadian rhythms are regulated by the direct influence of environmental input (light, food, activity), as well as the cell autonomous transcriptional mechanism known as the circadian clock. While circadian rhythms (and their disruption) are implicated in various cardiovascular disease states and IR-injury (with increased incidence and severity in the early morning), more recent attention has been directed toward the circadian regulation of myocardial preconditioning. Indeed, intact circadian rhythms, which are modulated by physical activity, are a cornerstone of health. As such, exercise may play an important role as a cardioprotective, and chronoprotective intervention. However, the circadian timing of interventions eliciting cardioprotection has not been explored. Thus, it is the purpose of this novel review to highlight cardioprotective mechanisms that are directly and indirectly controlled or influenced by the circadian rhythm, concluding with the perspective that preconditioning the heart may be optimally timed based on the circadian rhythm for maximal efficacy.
Cardiovascular Diseases | Diseases | Medicine and Health Sciences
McGinnis, G. R.,
Quindry, J. C.
Time to Exercise: Circadian Regulation of Cardiac Preconditioning.
Conditioning Medicine, 3(2),