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DOI: 10.3791/65233-v
The present protocol describes a large animal exercise test model to assess the functional capacity of the cardiovascular system for evaluating the efficiency of new therapies in the preclinical setting. It is comparable to a clinical exercise test.
The aim of the study is to provide a reliable exercise test for pigs that can be used to evaluate the safety and functional efficacy of gene therapy and other novel therapies. Usually, cardiovascular animal studies emphasize easily quantifiable endpoints just as capillary area calculated from the histological sections. In contrast, clinical studies use more subjective endpoints just as excess tolerance.
This protocol better matches the endpoints between preclinical and clinical studies. The previously published methods with longer running sessions aimed to evaluate chronic exercise adaptations, whereas the presented method is more suitable for evaluating cardiorespiratory fitness. To begin, set up a one-way running track using gates and hinges to prevent the back movement of the pigs.
Place a sheet of transparent plastic as a front wall to the treadmill. Place an ECG monitor and a defibrillator next to the treadmill. Let the pigs acclimatize to the setup by keeping the gates open so that they can walk free on the track and explore the environment.
When the animals have adjusted, turn the treadmill on and let the animals run for short durations, such as seven minutes. Place ECG electrodes in low movement locations on the pig's body, such as the scapulas or the chest. Turn the treadmill on and set the incline at 5 to 10%Begin with a speed of two kilometers per hour when the animal is on the treadmill.
Increase the speed by 0.5 kilometers per hour every minute until five kilometers per hour is attained. If the animal is not running at the desired speed, give it a gentle nudge from the back. Record the heart changes during the run.
Record the run distance, total time and speed every time the speed is changed. The animal's lacking motivation stopped running completely, whereas the fatigued animals reduced their speed but kept running. Exercise tolerance was lower in the animals with reduced dejection fractions, resulting in reduced speed throughout the exercise.
ECG showed a heart rate of 176 beats per minute three minutes after beginning the test. The heartbeat increased to 250 beats per minute 10 minutes after running.
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