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      Guidelines for animal exercise and training protocols for cardiovascular studies

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          Abstract

          Whole body exercise tolerance is the consummate example of integrative physiological function among the metabolic, neuromuscular, cardiovascular, and respiratory systems. Depending on the animal selected, the energetic demands and flux through the oxygen transport system can increase two orders of magnitude from rest to maximal exercise. Thus, animal models in health and disease present the scientist with flexible, powerful, and, in some instances, purpose-built tools to explore the mechanistic bases for physiological function and help unveil the causes for pathological or age-related exercise intolerance. Elegant experimental designs and analyses of kinetic parameters and steady-state responses permit acute and chronic exercise paradigms to identify therapeutic targets for drug development in disease and also present the opportunity to test the efficacy of pharmacological and behavioral countermeasures during aging, for example. However, for this promise to be fully realized, the correct or optimal animal model must be selected in conjunction with reproducible tests of physiological function (e.g., exercise capacity and maximal oxygen uptake) that can be compared equitably across laboratories, clinics, and other proving grounds. Rigorously controlled animal exercise and training studies constitute the foundation of translational research. This review presents the most commonly selected animal models with guidelines for their use and obtaining reproducible results and, crucially, translates state-of-the-art techniques and procedures developed on humans to those animal models.

          Listen to this article’s corresponding podcast at: https://ajpheart.podbean.com/e/guidelines-for-animal-exercise-and-training-protocols/ .

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          Most cited references416

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          Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1.

          Endurance exercise induces increases in mitochondria and the GLUT4 isoform of the glucose transporter in muscle. Although little is known about the mechanisms underlying these adaptations, new information has accumulated regarding how mitochondrial biogenesis and GLUT4 expression are regulated. This includes the findings that the transcriptional coactivator PGC-1 promotes mitochondrial biogenesis and that NRF-1 and NRF-2 act as transcriptional activators of genes encoding mitochondrial enzymes. We tested the hypothesis that increases in PGC-1, NRF-1, and NRF-2 are involved in the initial adaptive response of muscle to exercise. Five daily bouts of swimming induced increases in mitochondrial enzymes and GLUT4 in skeletal muscle in rats. One exercise bout resulted in approximately twofold increases in full-length muscle PGC-1 mRNA and PGC-1 protein, which were evident 18 h after exercise. A smaller form of PGC-1 increased after exercise. The exercise induced increases in muscle NRF-1 and NRF-2 that were evident 12 to 18 h after one exercise bout. These findings suggest that increases in PGC-1, NRF-1, and NRF-2 represent key regulatory components of the stimulation of mitochondrial biogenesis by exercise and that PGC-1 mediates the coordinated increases in GLUT4 and mitochondria.
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            Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure.

            Optimal timing of cardiac transplantation in ambulatory patients with severe left ventricular dysfunction is often difficult. To determine whether measurement of peak oxygen consumption (VO2) during maximal exercise testing can be used to identify patients in whom transplantation can be safely deferred, we prospectively performed exercise testing on all ambulatory patients referred for transplant between October 1986 and December 1989. Patients were assigned into one of three groups on the basis of exercise data: Group 1 (n = 35) comprised patients accepted for transplant (VO2 less than or equal to 14 ml/kg/min); group 2 (n = 52) comprised patients considered too well for transplant (VO2 greater than 14 ml/kg/min); and group 3 (n = 27) comprised patients with low VO2 rejected for transplant due to noncardiac problems. All three groups were comparable in New York Heart Association functional class, ejection fraction, and cardiac index (p = NS). Pulmonary capillary wedge pressure was significantly lower in group 2 than in either group 1 or 3 (p less than 0.05), although there was wide overlap. Patients with preserved exercise capacity (group 2) had cumulative 1- and 2-year survival rates of 94% and 84%, which are equal to survival levels after transplantation. In contrast, patients rejected for transplant (group 3) had survival rates of only 47% at 1 year and 32% at 2 years, whereas patients awaiting transplantation (group 1) had a survival rate of 70% at 1 year (both p less than 0.005 versus patients with VO2 greater than 14 ml/kg/min). All deaths in group 2 were sudden. By univariate and multivariate analyses, peak VO2 was the best predictor of survival, with only pulmonary capillary wedge pressure providing additional prognostic information. These data suggest that cardiac transplantation can be safely deferred in ambulatory patients with severe left ventricular dysfunction and peak exercise VO2 of more than 14 ml/min/kg.
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              Development and validation of a questionnaire for measuring behavior and temperament traits in pet dogs.

              To develop and validate a questionnaire to assess behavior and temperament traits of pet dogs. Cross-sectional survey of dog owners. Animals-1,851 dogs belonging to clients of a veterinary teaching hospital or members of national breed clubs and 203 dogs examined by canine behavior practitioners because of behavior problems. Owners were asked to complete a questionnaire consisting of 152 items eliciting information on how dogs responded to specific events and situations in their usual environment. Data from completed questionnaires were subjected to factor analysis, and the resulting factors were tested for reliability and validity. Factor analysis yielded 11 factors from 68 of the original questionnaire items that together accounted for 57% of the common variance in questionnaire item scores. Reliability was acceptable for all but 1 of these factors. Behavior problems in 200 of the 203 dogs with behavior problems could be assigned to 7 diagnostic categories that matched 7 of the factors identified during factor analysis of questionnaire responses. Dogs assigned to particular diagnostic categories had significantly higher scores for corresponding questionnaire factors than did those assigned to unrelated diagnostic categories, indicating that the factors were valid. Validity of the remaining 4 factors could not be examined because of a lack of information on dogs with behavior problems related to these factors. Findings suggest that the resulting 68-item questionnaire is a reliable and valid method of assessing behavior and temperament traits in dogs. The questionnaire may be useful in screening dogs for behavior problems and in evaluating the clinical effects of various treatments for behavior problems.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                American Journal of Physiology-Heart and Circulatory Physiology
                American Journal of Physiology-Heart and Circulatory Physiology
                American Physiological Society
                0363-6135
                1522-1539
                May 01 2020
                May 01 2020
                : 318
                : 5
                : H1100-H1138
                Affiliations
                [1 ]Department of Kinesiology, Kansas State University, Manhattan, Kansas
                [2 ]Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas
                [3 ]Department of Internal Medicine, University of Utah, Salt Lake City, Utah
                [4 ]Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, Salt Lake City, Utah
                [5 ]Department of Psychology and Neuroscience, University of Colorado, Boulder, Colorado
                [6 ]Department of Anatomy, Cell Biology and Physiology, Indiana University, Indianapolis, Indiana
                [7 ]Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan
                [8 ]Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska
                Article
                10.1152/ajpheart.00697.2019
                32196357
                9af927ca-346e-4885-838f-8879c178dcff
                © 2020
                History

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