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6 Challenges
6.1 Animals Models
Notably, most studies available on exercise-induced cardioprotection are under-
taken in experimental settings, where myocardium injury is caused in animals with-
out established cardiovascular diseases. In other words, so far the cardioprotective
effect of exercise against IRI has never been studied in animals presenting cardio-
vascular risk factors or diseases, such as hypertension, CAD or previous myocardial
infarct. On the other hand, ischemic heart disease in humans is a complex disorder,
which is usually caused by the combination of several cardiovascular risk factors
and comorbidities (e.g. diabetes, heart failure, hypertension, altered coronary circu-
lation and hyperlipidemia). These conditions together with the medications used
against them lead to important changes in cellular signaling cascades that interfere
in IRI and physiological responses to cardioprotective interventions, including exer-
cise [ 123 ].
Importantly, it has been shown in animal models of myocardial infarction thatvarious comorbidities, including hyperlipidemia and heart failure, can limit the effi-
cacy of ischemic preconditioning and postconditioning [ 59 , 123 , 124 ]. Therefore, it
is reasonable to assume that exercise-induced cardioprotection could also be
affected in the presence of comorbidities. However, data in this sense are scarce. To
the best of our knowledge, there is only one study that has focused on this issue
[ 125 ]. In this study, rats with type 1 diabetes mellitus underwent global ischemia
and reperfusion following resistance training or low-intensity aerobic training or
high-intensity aerobic training. The authors concluded that exercise-related cardio-
vascular protection was dependent on the exercise modality, whereby high-intensity
aerobic-exercised diabetic rats demonstrated the greatest myocardial recovery
against IRI. Unfortunately, as the authors did not include a nondiabetic exercised
group, conclusions regarding the changes in exercise-induced cardioprotection due
to diabetes per se cannot be made.
6.2 Translating Exercise-Induced Cardioprotection to Clinical
Practice
To achieve exercise-induced cardioprotection, exercise intervention is required
before a cardiac insult, which obviously cannot be predicted in humans, making
clinical research even more difficult. This explains why most data on this matter is
based on experimental research with animals.
However, to establish associations and clinical implications, a bulk of evidencehas demonstrated a phenomenon known as “warm-up” or exercise-induced isch-
emic preconditioning, in which exercise-induced ST-segment changes of patients
10 Cardiac Ischemia/Reperfusion Injury: The Bene cial Effects of Exercise