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

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In dynamic exercise training, heart rate ranged from 62 ± 4 (beats per minute,

minimum) to 254 ± 9 (beats per minute, maximum); while in untrained group, this

value ranged between 91  ±  13 and 273  ±  6 (beats per minute) [ 77 ]. Swine can

increase their heart rates from approximately 128–219% during exercise which can

be attributed to a large heart rate [ 13 , 76 ]; this value is very similar to the 140–170%

which are available in humans [ 78 ]. Chronic exercise affects swine cardiac cate-

cholamines and enkephalins, suggesting responsiveness to autonomic control and

its capability to alter cardiac function [ 16 ]. Another exercise research used mini

swines (pigs) as study subjects. In this study, down-regulation of ß- adrenergic

receptor was linked with training-associated decreases in heart rate [ 77 ]. In another

research, swine were employed to test for the effects of post-infarction mitral regur-

gitation during surgical repair [ 79 ] revealing that chronic exercise suppressed ß-

adrenergic receptors in the right atrium and is related with reduced chronotropic

responses to exercise and isoproterenol stimulation [ 77 ]. Pigs have been well char-

acterized as an appropriate model for the study of coronary physiology. Pigs have

been utilized as models of myocardial ischemia and myocardial infarction during

graduated treadmill exercise training and increased oxygen demand [ 80 ]. These ani-

mals are also the best subjects for investigating the coronary collateral circulation

and exercise physiology and pathophysiology [ 75 , 80 ]. Taken together, the swine or

pig has proven its value for pre-clinical research due to its similarities with the

human cardiovascular system, and its characteristically large heart and body weight.

3.3.5 Sheep

Similarly with other large animals, the sheep share numerous similarities with

humans which makes it a good pre-clinical model to study cardiovascular diseases

[ 7 ], including myocardial infarction [ 81 ], gradual aortic constriction [ 82 ], and

tachypacing induced heart failure [ 4 ].

Although disadvantageous when it comes to cost and maintenance, sheep-

subjected disease models will generally better recapitulate changes in humans and

efficacy of novel therapeutic avenues than small animal models [ 6 ]. The previous

studies [ 45 , 47 , 83 ] demonstrated that maternal exercise (treadmill) decrease uterine

blood flow [ 45 ] but does not pose a stressful (e.g. hypoxic) event to the fetus as

evidenced by blood gases, temperatures, and fetal cardiovascular system assess-

ment [ 47 ]. The data proved that relatively constant oxygen delivery to the uterus

was managed by means of hemoconcentration adaptation during exercise [ 45 ]. Thus

redistribution flow towards the placenta after exercise might be a fetal compensa-

tory mechanism [ 83 ].

Because of their historical use in cardiovascular research and because of their

suitability in investigating pathways involved in pediatric heart-valve calcification,

sheep have been widely used as the model of choice for cardiopulmonary bypass

procedures [ 7 ]. Also, sheep are appropriate subjects to study clinically ischemic

mitral regurgitation occurring in myocardial infarction-induced left ventricular

remodeling [ 35 ]. The evidence showed that annuloplasty provides durable relief

V.T. Thu et al.