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

Avaliação da tolerância ao exercício de suínos submetidos ao exercício

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.

Autor em destaque: Teste ergométrico para avaliação da eficácia funcional do sistema cardiovascular suíno  

Teste Ergométrico para Avaliação da Eficácia Funcional do Sistema Cardiovascular de Suínos

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  

Avaliação da tolerância ao exercício de suínos submetidos a teste de exercício: configuração da pista e monitoramento do exercício suíno

Para começar, monte uma pista de corrida de mão única usando portões e dobradiças para evitar o movimento de costas dos porcos. Coloque uma folha de plástico transparente como parede frontal para a esteira. Coloque um monitor de ECG e um desfibrilador ao lado da esteira.Deixe os porcos se aclimatarem ao local, mantendo os portões abertos para que possam andar livres na pista e explorar o ambiente. Quando os animais tiverem se ajustado, ligue a esteira e deixe os animais correrem por curtas durações, como sete minutos. Coloque eletrodos de ECG em locais de baixo movimento no corpo do porco, como as escápulas ou o peito.Ligue a esteira e ajuste a inclinação em 5 a 10%Comece com uma velocidade de dois quilômetros por hora quando o animal estiver na esteira. Aumente a velocidade em 0,5 quilômetros por hora a cada minuto até atingir cinco quilômetros por hora. Se o animal não estiver correndo na velocidade desejada, dê um empurrão suave nas costas.Registre as mudanças cardíacas durante a corrida. Registre a distância de corrida, o tempo total e a velocidade sempre que a velocidade for alterada. Os animais sem motivação pararam de correr completamente, enquanto os animais cansados reduziram sua velocidade, mas continuaram correndo.A tolerância ao exercício foi menor nos animais com fração de ejeção reduzida, resultando em velocidade reduzida ao longo do exercício. O ECG mostrou frequência cardíaca de 176 batimentos por minuto três minutos após o início do teste. Os batimentos cardíacos aumentaram para 250 batimentos por minuto, 10 minutos após a corrida.

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 visualizações.  University of Eastern Finland. Para começar, monte uma pista de corrida de mão única usando portões e dobradiças para evitar o movimento de costas dos porcos. Coloque uma folha de plástico transparente como parede frontal para a esteira. Coloque um monitor de ECG e um desfibrilador ao lado da esteira.Deixe os porcos se aclimatarem ao local, mantendo os portões abertos para que possam andar livres na pista e explorar o ambiente. Quando os animais tiverem se ajustado, ligue a esteira e deixe os animais correrem...

Vídeo: 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 ...

Genética

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.