Short-term exercise-induced protection of cardiovascular function and health: why and how fast does the heart benefit from exercise?

Abstract

Regular exercise training has potent and powerful protective effects against the development of cardiovascular disease. These cardioprotective effects of regular exercise training are partly explained through the effects of exercise on traditional cardiovascular risk factors and improvement in cardiac and vascular health, which take several weeks to months to develop. This review focuses on the observation that single bouts of exercise may also possess an underrecognized, clinically useful form of immediate cardioprotection. Studies, performed in both animals and humans, demonstrate that single or short-term exercise-induced protection (SEP) attenuates the magnitude of cardiac and/or vascular damage in response to prolonged ischaemia and reperfusion injury. This review highlights preclinical evidence supporting the hypothesis that SEP activates multiple pathways to confer immediate protection against ischaemic events, reduce the severity of potentially lethal ischaemic myocardial injury, and therefore act as a physiological first line of defence against injury. Given the fact that the extent of SEP could be modulated by exercise-related and subject-related factors, it is important to recognize and consider these factors to optimize future clinical implications of SEP. This review also summarizes potential effector signalling pathways (i.e. communication between exercising muscles to vascular/cardiac tissue) and intracellular pathways (i.e. reducing tissue damage) that ultimately confer protection against cardiac and vascular injury. Finally, we discuss potential future directions for designing adequate human and animal studies that will support developing effective SEP strategies for the (multi-)diseased and aged individual. KEY POINTS: Single or short-term exercise-induced protection (SEP) attenuates the magnitude of cardiac and/or vascular damage in response to prolonged ischaemia and reperfusion injury (IR injury). SEP activates multiple pathways to confer cardiac protection, which develops remotely at the site of the activated muscle by release of circulating molecules, which transfer towards activation of intramyocardial signalling that promotes cell survival during episodes of IR injury. SEP represents an attractive intervention in aged individuals and in those with co-morbidities. The immediate protection, low cost and simplicity to increase the 'dose' of SEP offers unique opportunities in the clinical applications of SEP.

Keywords: cardioprotection; ischaemia reperfusion injury; ischaemic heart disease; single exercise-induced protection.

Figure 1. Overview of benefits of short‐term and habitual exercise in the prevention of cardiovascular disease

Single or short‐term exercise‐induced protection (SEP) against ischaemia–reperfusion (IR) injury may lessen the severity of myocardial injury from cardiac surgery or myocardial infarction, while habitual exercise training (days–years) leads to physiological adaptions and changes in traditional cardiovascular disease (CVD) risk factors that may prevent the occurrence of a cardiac event.

Figure 2. Proposed modulators of short‐term exercise‐induced protection (SEP)

Exercise stimulus (intensity, mode) and subject‐related factors (ageing, prior training status, disease risk factors) may influence the magnitude of exercise‐induced cardioprotection against myocardial injury.

Figure 3. Proposed effector signalling and intracellular mechanisms of SEP

Release of myokines, metabolites, humoral factors, cytokines and ROS in the circulatory system by exercise modulates intramyocardial signalling during IR, contributing to reduced inflammation and apoptosis, increased anti‐scavenging processes and K_ATP channel activation, which ultimately result in protection against cardiac cell death.