Changes in microarchitecture of atherosclerotic calcification assessed by 18F-NaF PET and CT after a progressive exercise regimen in hyperlipidemic mice.

BACKGROUND: Despite the association of physical activity with improved cardiovascular outcomes and the association of high coronary artery calcification (CAC) scores with poor prognosis, elite endurance athletes have increased CAC. Yet, they nevertheless have better cardiovascular survival. We hypothesized that exercise may transform vascular calcium deposits to a more stable morphology. METHODS: To test this, hyperlipidemic mice (Apoe-/-) with baseline aortic calcification were separated into 2 groups (n = 9/group) with control mice allowed to move ad-lib while the exercise group underwent a progressive treadmill regimen for 9 weeks. All mice underwent blood collections and in vivo 18F-NaF µPET/µCT imaging both at the start and end of the exercise regimen. At euthanasia, aortic root specimens were obtained for histomorphometry. RESULTS: Results showed that, while aortic calcification progressed similarly in both groups based on µCT, the fold change in 18F-NaF density was significantly less in the exercise group. Histomorphometric analysis of the aortic root calcium deposits showed that the exercised mice had a lower mineral surface area index than the control group. The exercise regimen also raised serum PTH levels twofold. CONCLUSION: These findings suggest that weeks-long progressive exercise alters the microarchitecture of atherosclerotic calcium deposits by reducing mineral surface growth, potentially favoring plaque stability.

Measuring the Effects of Circadian Rhythm-Related Manipulations on Depression-Like Behavior in Rodents: Forced Swim and Tail Suspension Tests.

The forced swim and tail suspension tests are commonly used to determine the effects of circadian-related pharmacological, genetic, and environmental manipulations on depression-like behavior in rodents. Both tests involve scoring immobility of rodents in an inescapable condition. Here we describe how to set up and carry out these tests.

Guidelines for animal exercise and training protocols for cardiovascular studies.

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.

A Comparison of Two Mouse Frailty Assessment Tools.

The mouse clinical frailty index and the mouse frailty phenotype assessment are two recently developed tools used to assess frailty in mice. The objectives of this study were to investigate whether the same mice are identified as frail with both tools and to examine the association of each of the assessment tools with age and frailty-related outcomes. Frailty was measured using both tools in old (~24 months; n = 36) C57BL/6 male mice. After 2 weeks, blood pressure and heart rate were measured and serum samples were collected for analysis of alanine aminotransferase, creatinine, and albumin levels. The mouse frailty phenotype assessment identified no mice as frail but modification of the assessment tool identified six mice as frail. The mouse clinical frailty index identified 16 mice as frail and the agreement between the two scales was 50.0%. Increasing clinical frailty index scores were correlated with low serum alanine aminotransferase, as well as decreased heart rate, and reduced heart rate variance. We conclude that, consistent with equivalent frailty assessment scales in humans, both tools have value but do not necessarily identify the same mice as frail.

Development of a Rat Clinical Frailty Index.

Rats are a commonly used model for aging studies, and a frailty assessment tool for rats would be of considerable value. There has been a recent focus on the development of preclinical models of frailty in mice. A mouse clinical frailty index (FI) was developed based on clinical frailty assessment tools. This FI measures the accumulation of clinically evident health-related deficits in mice. This paper aimed to develop a rat clinical FI. Male Fischer 344 rats were aged from 6 to 9 months (n = 12), and from 13 to 21 months (n = 41). A FI comprised of 27 health-related deficits was developed from a review of the literature and consultation with a veterinarian. Deficits were scored 0 if absent, 0.5 if mild, or 1 if severe. A FI score was determined for each rat every 3-4 months, and for the older group mortality was assessed up to 21 months. Mean FI scores significantly increased at each time point for the older rats. A high FI score measured at both 17 months of age and terminally was also associated with decreased probability of survival as assessed with Kaplan-Meier curves. The rat clinical FI has significant value for use in aging and interventional studies.

Cardiac Mean Electrical Axis in Thoroughbreds-Standardization by the Dubois Lead Positioning System.

BACKGROUND: Different methodologies for electrocardiographic acquisition in horses have been used since the first ECG recordings in equines were reported early in the last century. This study aimed to determine the best ECG electrodes positioning method and the most reliable calculation of mean cardiac axis (MEA) in equines. MATERIALS AND METHODS: We evaluated the electrocardiographic profile of 53 clinically healthy Thoroughbreds, 38 males and 15 females, with ages ranging 2-7 years old, all reared at the São Paulo Jockey Club, in Brazil. Two ECG tracings were recorded from each animal, one using the Dubois lead positioning system, the second using the base-apex method. QRS complex amplitudes were analyzed to obtain MEA values in the frontal plane for each of the two electrode positioning methods mentioned above, using two calculation approaches, the first by Tilley tables and the second by trigonometric calculation. Results were compared between the two methods. RESULTS: There was significant difference in cardiac axis values: MEA obtained by the Tilley tables was +135.1° ± 90.9° vs. -81.1° ± 3.6° (p<0.0001), and by trigonometric calculation it was -15.0° ± 11.3° vs. -79.9° ± 7.4° (p<0.0001), base-apex and Dubois, respectively. Furthermore, Dubois method presented small range of variation without statistical or clinical difference by either calculation mode, while there was a wide variation in the base-apex method. CONCLUSION: Dubois improved centralization of the Thoroughbreds' hearts, engendering what seems to be the real frontal plane. By either calculation mode, it was the most reliable methodology to obtain cardiac mean electrical axis in equines.

Exercise testing in Warmblood sport horses under field conditions.

Regular exercise testing in Warmblood sport horses may, as in racing, potentially help to characterise fitness indices in different disciplines and at various competition levels and assist in understanding when a horse is 'fit to compete'. In this review an overview is given of the current state of the art of exercise testing in the Olympic disciplines of eventing, show jumping and dressage, and areas for further development are defined. In event horses, a simple four-step incremental exercise test measuring heart rate (HR), lactate concentration (LA) and velocity (V) is most often used. In dressage and riding horses, a wide variety of exercise tests have been developed, including incremental exercise tests, indoor riding tests and lunging tests. In show jumping, the use of a five-step incremental exercise test and exercise tests evaluating technical skills and fatigue of the horse has been reported. The velocity at a plasma LA of 4 mmol/L (VLA4) and HR recovery during submaximal exercise intensity have been shown to be the best parameters in event horses for predicting performance and impending injuries. In riding horses, the fitness level of horses is also an important determinant of injuries. Implementation of regular exercise testing and monitoring of training sessions may have important added value in the assessment of performance ability and potential future injuries in Warmblood sport horses. However, there is an urgent need to standardise methodologies and outcome parameters in order to make results comparable.

Can we optimise the exercise training prescription to maximise improvements in mitochondria function and content?

BACKGROUND: While there is agreement that exercise is a powerful stimulus to increase both mitochondrial function and content, we do not know the optimal training stimulus to maximise improvements in mitochondrial biogenesis. SCOPE OF REVIEW: This review will focus predominantly on the effects of exercise on mitochondrial function and content, as there is a greater volume of published research on these adaptations and stronger conclusions can be made. MAJOR CONCLUSIONS: The results of cross-sectional studies, as well as training studies involving rats and humans, suggest that training intensity may be an important determinant of improvements in mitochondrial function (as determined by mitochondrial respiration), but not mitochondrial content (as assessed by citrate synthase activity). In contrast, it appears that training volume, rather than training intensity, may be an important determinant of exercise-induced improvements in mitochondrial content. Exercise-induced mitochondrial adaptations are quickly reversed following a reduction or cessation of physical activity, highlighting that skeletal muscle is a remarkably plastic tissue. Due to the small number of studies, more research is required to verify the trends highlighted in this review, and further studies are required to investigate the effects of different types of training on the mitochondrial sub-populations and also mitochondrial adaptations in different fibre types. Further research is also required to better understand how genetic variants influence the large individual variability for exercise-induced changes in mitochondrial biogenesis. GENERAL SIGNIFICANCE: The importance of mitochondria for both athletic performance and health underlines the importance of better understanding the factors that regulate exercise-induced changes in mitochondrial biogenesis. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.

Standardization of an experimental model suitable for studies on the effect of exercise on arthritis.

OBJECTIVE: To standardize an experimental model of chronic monoarthritis induced by complete Freund's adjuvant appropriate for the analysis of the effect of walking on nociception and on joint edema. METHODS: The following factors were evaluated as to monoarthritis induction: route and site of administration, number and interval of inoculations, Mycobacterium species, and animal gender. Wistar male and female rats (200 to 250g) received two injections of complete Freund's adjuvant containing Mycobacterium tuberculosis (1.0mg/mL; 50µL) or Mycobacterium butyricum (0.5mg/mL; 50µL) intra-articularly in the tibiotarsal or tibiofemoral joints, or an injection of complete Freund's adjuvant (Mycobacterium butyricum or tuberculosis) intradermally at the base of the tail and another intra-articularly (tibiotarsal or tibiofemoral). The animals were submitted to evaluations of articular disability and edema. Articular disability was assessed by paw elevation time (in seconds) during the one-minute walk test. Edema of the tibiofemoral joint was assessed by variation of joint diameter (cm). Tibiotarsal joint edema was measured by the volume of the paw (mL). RESULTS: Administration of complete Freund's adjuvant containing Mycobacterium butyricum increased paw elevation time and edema in both joints. CONCLUSIONS: These data allow standardization of an animal model of chronic monoarthritis adequate for analysis of the effects of exercise on treatment of rheumatoid arthritis.

Preliminary evaluation of a quality-of-life screening programme for pet dogs.

OBJECTIVES: To evaluate a potential screening programme that would raise awareness of welfare consideration of pet dogs visiting a veterinary practice. METHODS: The questionnaire asked owners to provide biographical information about their dog, assess the resources they provided their dog (comfort, exercise, diet, mental stimulation and companionship) from the perspective of their dog's wellbeing and choice, score a range of behavioural and medical signs on visual analogue scale, rate how willing they would be to take on the life of their dog on a visual analogue scale and suggest changes that would improve the quality of life of their dog. RESULTS: Twenty-seven owners completed the questionnaire on consecutive days. There was good correlation for all the parameters between the two days (P<0.05). Of the 16 expected correlations to test internal consistency, nine were significant (P<0.05). Twenty-six per cent of owners scored in the top 10 mm of the visual analogue scale for being willing to "take on the life their dog was living". More exercise was the most commonly suggested change to improve quality of life (14 owners). CLINICAL SIGNIFICANCE: The questionnaire was found to be repeatable, feasible and to have good internal consistency and validity, making it suitable for use in veterinary practice to assess welfare.