Exercise for Cardiovascular Disease Prevention and Treatment From Molecular to Clinical, Part 1

145

put, biological system alters the autonomic control of the heart and vessels favouring

the sympathetic activity, thus increasing cardiac chronotropism (frequency) and inot-

ropism (strength), as well as the activity of molecules associated with adrenergic

control as catecholamines and RAAS [ 8 ]. Even if such alterations act beneficially in

the first hours after MI  – collaborating to maintain blood perfusion to the tissues,

and, consequently, nutrients delivery - over time these compensatory alterations will

cause several malefic alterations in cardiac functioning and structure [ 8 , 30 ].

ROS activity is increased from the early remodelling phase to the late remodelling

phase in response to cardiac ischemia with or without reperfusion [ 21 , 31 , 32 ]. ROS

synthesis and release are induced by several elements showed in the ischemic myo-

cardium including, but not limited to proinflammatory citokynes and RAAS [ 29 , 30 ,

32 ]. Once activated, ROS pathway will act triggering alterations on cardiomyocyte,

collaborating, for example, with cardiac hypertrophy induced by proinflammatory

citokynes and RAAS [ 30 ]. On the other hand, activity of different elements of the

antioxidant milieu (e.g., vitamin E, catalase, superoxide dismutase [SOD]) seems to

successfully inhibit such alterations induced by ROS [ 21 , 30 ]. Indeed, the myocar-

dium of transgenic animals overexpressing SOD shows abolished free radical gen-

eration, ameliorated recovery of contraction function and lower infarcted area after

ischemia-reperfusion, in comparison with wild-type animals [ 20 , 21 ].

Even if there are no evidence indicating the effects of ET posterior to MI in the

early remodelling phase, an isolated result showed that 12 weeks of low-to- moderate

aerobic exercise performed during 50  min, 5  days per week previously to MI

induced by isoproterenol was effective to decreased infarction degree and ROS

expression and activity in the heart of the trained rats in comparison with sedentary

animals. Concomitantly, the authors observed decreased activity of antioxidant

enzymes, as superoxide dismutase and catalase in the heart of sedentary rats.

However, ET could attenuate this phenomenon [ 31 ]. However, the study did not

accomplish additional analyses, as cardiac functioning, and inferences about the

data are limited.

As abovementioned, besides its association with ROS, proinflammatory cito-

kynes have a marked influence on MMPs [ 29 , 33 ]. Immediately after myocardial

injury caused by ischemia, neutrophils migrate to the MI area and recruit MMPs,

which induce collagen breakdown [ 29 ]. This phenomenon will induce fibroblast

migration and, posterior, differentiation in myofibroblasts, which are crucial to

fibrotic tissue formation (i.e., scar) [ 29 , 33 ]. In summary, myofibroblasts causes

accumulation of matrix collagen fibers, glycoprotein fibronectin, type III collagen

replaced by type I collagen, formation of the fibrin clot and collagen-based scar [ 33 ].

Experiments have been indicating that ET can modulate this response, since ET

performed previous and after MI reduces the components of the ECM remodelling.

Bozi et  al. [ 34 ], for instance, observed that 8  weeks of moderate ET previous to

experimental MI decreased collagen content in the heart of rats. In relation to post-

MI effects, Xu et al. [ 22 ] and Yengo et al. [ 35 ], showed that moderate ET performed

during 8 and 10 weeks, respectively, decrease the collagen volume and content in

the infarcted area. Moreover, further analyses of Xu et  al. [ 22 ], evaluated non-

reducible collagen cross-linking (hydroxylysyl pyridinoline, HP) content - a marker

9 Myocardial Infarction and Exercise Training: Evidence from Basic Science