65
though other large species of animals such as canine, pigs, and sheep are more similar
to the human heart, the cost for managing rabbits is significantly much lower [ 3 ].
Despite a close similarity to humans [ 71 ], the differences between rabbit and human
myocardium result in differential effects in a particular study or therapeutic interven-
tion. Overall, rabbits are practical and efficient as a model for cardiovascular studies.
3.3.3 Canine Models
Canine and human hearts have similar characteristics both at organ and cellular
levels. As previously summarized, canine heart rate, body weight, and heart weight
which are more similar to humans than smaller models such as mice, rats, and rab-
bits [ 3 , 6 ]. Importantly, changes in the heart rates and other hemodynamic parame-
ters are similar between canines and humans [ 3 ]. The shape of the force-frequency
relationship is a lot closer to humans compared to mice, rats, and rabbits [ 5 , 14 , 15 ].
These characteristics make both myocardial models react similarly in response to
exercise [ 6 ]. Typically, canines can significantly increase its heart rate of approxi-
mately 96–136% during maximal exercise [ 72 , 73 ].
Moreover, canines are commonly used for studies utilizing exercise in cardiovas-cular abnormalities, including ischemic heart disease [ 16 , 36 ]. Endurance exercise
training can enhance cardiac electrical stability in subjects at higher risk for sudden
cardiac death [ 5 , 16 , 74 ]. Canines were also used for sudden death to study the
effects of daily training on cardiac regulation and remodeling. In dogs, daily exer-
cise affects autonomic control of the heart and prevents ventricular filtration induced
by acute myocardial ischemia [ 19 ]. Endurance exercise training (treadmill running)
interestingly is the most effective antiarrhythmic therapy in the canine model of
sudden death, the effect of which was conferred by the prevention of ventricular
fibrillation after endurance training program [ 5 , 74 ]. The amelioration of treadmill
exercise-induced myocardial ischemia was brought about by the enhancement of
coronary vasodilator reserve in dogs [ 72 ]. During resting state, coronary vasodilator
reserve occurs even in the presence of myocardial ischemia [ 72 ]. Another study
using calcium-entry blocker diltiazem in conscious dogs improved both regional
myocardial flow and function during exercise, leading to a faster recovery of
regional myocardial dysfunction in a chronic coronary stenosis model [ 73 ]. It also
affects neuroendocrine transmitters partaking in autonomic regulation and signaling
of canine heart [ 16 ]. The exercise-induced change in autonomic tone to the heart
was different among species [ 16 ]. Overall, even considering the high cost disadvan-
tage, the canine myocardium serves as an appropriate model of human heart.
3.3.4 Swine
Many researches have used swine due to its similarity with excitation-contraction
coupling with human myocardium [ 13 , 16 , 75 – 77 ].
4 Acute and Chronic Exercise in Animal Models