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

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physiology and diseases [ 10 ]. Pre-clinical trial of cardiovascular pharmacology can

possibly be investigated using these small rodents efficiently and with relatively low

financial cost.

The most advantageous aspect of utilizing small rodents, such as mice, is the

allowance of several in vivo cardiac parameters to be measured by applying techno-

logical advances such as in making genetic models [ 31 , 43 , 58 ]. Cardiovascular

adaptation accompanied exercise training in experimental animal rodent models are

dependent on various applied factors such as duration, intensity, time, and frequency

[ 20 ]. With a motorized treadmill (with speed at 5, 10, 15, and 20 meters per minute

on a 10% grade for about 3 minutes at each workload), rats and mice can increase

their heart rates by ~40–50% and ~30–40%, respectively [ 59 ].

To study the positive effect or effect of exercise training on hearts, investigators

used different sample types like in vivo hearts [ 60 ], isolated hearts [ 61 ], cardiac

muscle [ 44 ], and isolated cardiomyocytes [ 62 ]. These studies have also focused on

cardiac functional changes induced by exhaustive exercise though echocardiogra-

phy [ 60 ] with changes in left ventricular hemodynamic recorded after an acute bout

of exhaustive exercise using pressure-volume analysis [ 30 ].

A number of rodent models in exercise-induced cardiac hypertrophy have been

made, and a number of endurance exercise trainings effectively induced animal car-

diac hypertrophy, such as treadmill running, voluntary wheel running, and swim

training [ 1 , 21 , 51 , 52 ]. When it comes to inducing physiological hypertrophy, swim

training seems to be as effective as treadmill or voluntary wheel running programs

[ 1 , 51 , 52 ]. Rat swimming model was used to study functional aspects of exercise-

induced hypertrophy in athlete’s heart [ 40 ]. Authors had demonstrated the potential

of assessing left ventricular function in exercise-induced cardiac hypertrophy. Data

showed reversible physiological cardiac hypertrophy induced by exercise in rats and

characterized cardiac systolic (improved contractility) and diastolic (improved

active relaxation and unchanged left ventricular stiffness) functional improvement

[ 40 ]. Although regular swim training was not associated with increased stress

response in chosen rat model, the results from the previous research is limited to

young male rats [ 40 ]. Rats were also chosen to develop animal model of swimming-

trained cardiac hypertrophy to study arrhythmias during an acute period of ischemia

[ 54 ]. In contrast, swim training of rats either reduced [ 54 ] or did not affect [ 49 ] the

susceptibility to ventricular fibrillation brought about by coronary artery occlusion.

Another study noted that endurance training protocols showed improvements as a

result of ventricular remodeling, enhanced contraction, and improved Ca2+ handling

in rats with experiment heart failure [ 63 ].

In mice, aerobic exercise may offer beneficial effects for coronary perfusion in

the myocardial ischemia area via calcitonin gene-related peptide changes [ 34 ].

Mouse cardio-metabolic phenotype models were generated to assess functional

cardiovascular fitness via graded maximal exercise testing [ 43 ]. Investigators also

developed a graded mouse maximal exercise test to improve testing sensitivity and

develop translatable parameters to assess functions of cardiovascular fitness in

healthy and dysfunctional mice with non-invasive and cost- effective methods [ 43 ].

microRNAs were previously found to be necessary players for cardiac growth

4 Acute and Chronic Exercise in Animal Models