The video outlines a procedure for conducting exercise tests on pigs using a treadmill. It details setting up the track, acclimatizing the animals, and monitoring their heart rates via ECG during exercise. Key findings include variations in exercise tolerance related to heart function, indicated by monitored heart rate changes throughout the activity.

evaluation of exercise tolerance of pigs subjected to exercise test: track setup and pig exercise monitoring

運動負荷豚の運動耐容性評価

Chronic cardiovascular diseases are significant causes of mortality and morbidity worldwide1,2. Although current treatments are effective for the majority of patients, many still cannot benefit from the current therapies due to, for example, diffuse chronic disease or comorbidities. In addition, in some patients, cardiac symptoms are not relieved by the available treatments, and their cardiovascular disease progresses despite optimal medical therapy3. Thus, there is a clear need to develop novel treatment options for severe cardiovascular diseases.
During the past several years, new molecular pathways and ways to manipulate these targets have been discovered, making gene therapy, cell therapy, and other novel therapies a realistic option for treating severe cardiovascular diseases4. However, after promising preclinical results, many cardiovascular applications have failed to fulfill expectations in clinical trials. In spite of the poor efficacy in clinical trials, several trials have established good safety profiles of novel therapies5,6,7,8,9. Thus, bringing new cardiovascular therapies to patients will require improved approaches and better preclinical models, study settings, and endpoints in preclinical studies that can predict clinical efficacy.
In animal models, the emphasis has usually been on easily quantifiable endpoints, such as the number and area of capillary vessels calculated from histological sections or parameters from left ventricle imaging at rest and under pharmacological stress. In clinical trials, many endpoints have been more subjective, such as exercise tolerance or symptom relief4. Thus, it is likely that the endpoints in preclinical studies and clinical trials measure different aspects of the applied therapy. For example, an increase in the quantity of blood vessels does not always correlate with better perfusion, cardiac function, or exercise tolerance. Nevertheless, both types of endpoints are required to develop successful therapeutic approaches10.&#160;Still, the main goal is always to alleviate symptoms and to improve the patient&#39;s prognosis and quality of life. To achieve this, endpoint measurements must be better matched between preclinical and clinical studies4.
Cardiorespiratory fitness reflects the ability of the circulatory and respiratory systems to provide oxygen during sustained physical activity, and thus it quantifies the functional capacity of an individual. Functional capacity is a key prognostic marker as it is a strong independent predictor for the risk of cardiovascular and all-cause mortality11. Improvements in cardiorespiratory fitness are associated with a reduced risk of mortality12. Exercise tests are suitable for evaluating aerobic performance and treatment responses in cardiovascular diseases. Depending on the availability, tests are performed on a bicycle ergometer or a treadmill. A gradual increase in the workload per minute is usually used, and abrupt increases are avoided; this leads to a linear physiological response. The most important variables in the exercise tests include the total exercise time, metabolic equivalents (METs) achieved, heart rate, and changes on an electrocardiogram (ECG) line between the QRS complex (Q, R, and S waves) and T-wave (ST segment). Clinical stress tests have low costs and are easily accessible13. For these reasons, stress tests, such as the 6 min walking test, have been widely used in clinics and should also be used in the preclinical evaluation of new therapies.
To our knowledge, there are no well-described large animal models for evaluating the functional efficacy of gene therapy or other novel therapies. Therefore, the clinically relevant exercise test provides an excellent perspective for evaluating the efficiency of these new therapies in the preclinical setting.

著者スポットライト:ブタ心血管系の機能的有効性を評価するための運動試験  

ブタ心血管系の機能的有効性評価のための運動試験

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 such as excess tolerance.This protocol better matches the endpoints between pre-clinical and clinical studies. The previously published methods with longer running sessions aim to evaluate chronic exercise adaptations, whereas the presented method is more suitable for evaluating cardio respiratory fitness.

Watch this Scientific Journal Video about Evaluation of Exercise Tolerance of Pigs Subjected to Exercise Test: Track Setup and Pig Exercise Monitoring at JoVE.com

Evaluation of Exercise Tolerance of Pigs Subjected to Exercise Test: Track Setup and Pig Exercise Monitoring  

運動試験を受けたブタの運動耐容能の評価:トラックのセットアップとブタの運動モニタリング

まず、豚の後ろの動きを防ぐために、ゲートとヒンジを使用して一方通行のランニングトラックを設定します。トレッドミルの前壁として透明なプラスチックのシートを置きます。トレッドミルの隣にECGモニターと除細動器を置きます。豚がトラックを自由に歩き、環境を探索できるように、ゲートを開いたままにして、豚をセットアップに順応させます。動物が順応したら、トレッドミルをオンにして、動物を7分などの短時間走らせます。肩甲骨や胸部など、ブタの体の動きの少ない場所にECG電極を配置します。トレッドミルをオンにし、傾斜を5〜10%に設定します動物がトレッドミルに乗っているときは、時速2キロメートルの速度から始めます。時速5キロメートルに達するまで、毎分時速0.5キロメートルずつ速度を上げます。動物が希望の速度で走っていない場合は、後ろからそっと動かします。ランニング中の心臓の変化を記録します。速度が変更されるたびに、走行距離、合計時間、速度を記録します。やる気のない動物は走るのを完全に止め、疲れた動物は速度を落としましたが、走り続けました。駆出率が低下した動物では運動耐容能が低く、運動中の速度が低下しました。ECGは、テスト開始から3分後に毎分176拍の心拍数を示しました。心拍は、走ってから10分後に毎分250拍に増加しました。

evaluation-exercise-tolerance-pigs-subjected-to-exercise-test-track

Research

JoVE Journal

Genetics

Evaluation of Exercise Tolerance of Pigs Subjected to Exercise Test: Track Setup and Pig Exercise Monitoring

264 ビュー.  University of Eastern Finland. まず、豚の後ろの動きを防ぐために、ゲートとヒンジを使用して一方通行のランニングトラックを設定します。トレッドミルの前壁として透明なプラスチックのシートを置きます。トレッドミルの隣にECGモニターと除細動器を置きます。豚がトラックを自由に歩き、環境を探索できるように、ゲートを開いたままにして、豚をセットアップに順応させます。動物が?...

ビデオ: Evaluation of Exercise Tolerance of Pigs Subjected to Exercise Test: Track Setup and Pig Exercise Monitoring  

Exercise Test for Evaluation of the Functional Efficacy of the Pig Cardiovascular System

Despite the progress in treatments, cardiovascular diseases are still one of the biggest causes of mortality and morbidity worldwide. Gene therapy-based therapeutic angiogenesis is a promising approach for treating patients with significant symptoms, despite optimal pharmacological therapy and invasive procedures. However, many promising cardiovascular gene therapy techniques have failed to accomplish expectations in clinical trials. One explanation is a mismatch between preclinical and clinical endpoints used to measure efficacy. In animal models, the emphasis has usually been on easily quantifiable endpoints, such as the number and area of the capillary vessels calculated from histological sections. Apart from mortality and morbidity, endpoints in clinical trials are subjective, such as exercise tolerance and quality of life. However, the preclinical and clinical endpoints likely measure different aspects of the applied therapy. Nevertheless, both types of endpoints are required to develop successful therapeutic approaches. In clinics, the main goal is always to alleviate patients' symptoms and improve their prognosis and quality of life. To achieve better predictive data from preclinical studies, endpoint measurements must be better matched to those in clinical studies. Here, we introduce a protocol for a clinically relevant treadmill exercise test in pigs. This study aims to: (1) provide a reliable exercise test in pigs that can be used to evaluate the safety and functional efficacy of gene therapy and other novel therapies, and (2) better match the endpoints between preclinical and clinical studies.

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.

Despite the progress in treatments, cardiovascular diseases are still one of the biggest causes of mortality and morbidity worldwide. Gene therapy-based ...

遺伝学

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 animals lacking motivation stopped running completely, whereas the fatigued animals reduced their speed, but kept running.Exercise tolerance was lower in the animals with reduced ejection 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.