Risk indictors in cats with preclinical hypertrophic cardiomyopathy: a prospective cohort study

Objectives This study aimed to identify indicators of the risk of progression of preclinical hypertrophic cardiomyopathy (HCM). Methods This was a prospective cohort study following a population of cats with preclinical HCM. Cats serially underwent physical examination, blood pressure measurement, blood sampling and echocardiography. Development of congestive heart failure (CHF), arterial thromboembolism (ATE) or sudden death (SD) were considered cardiac-related events. Associations between factors recorded at baseline, and on revisit examinations, and the development of a cardiac-related event were explored using receiver operator characteristic (ROC) analysis. Results Forty-seven cats were recruited to the study and were followed for a median period of 1135 days. Fifteen cats (31.9%) experienced at least one cardiac-related event; six CHF, five ATE and five SD. One cat experienced a cardiac-related event per 10.3 years of patient follow-up. Cats with increased left atrial (LA) size and higher concentrations of N-terminal pro B-type natriuretic peptide (NTproBNP) at baseline were more likely to experience an event. Cats with a greater rate of enlargement of LA size between examinations were also more likely to experience an event. Conclusions and relevance Factors easily measured, either once or serially, in cats with preclinical HCM can help to identify those at greater risk of going on to develop clinical signs

The IMPROVE guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments)

Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and animal welfare. It provides a number of recommendations to minimise the level of severity in the most common rodent models of middle cerebral artery occlusion, while sustaining or improving the scientific outcomes. The recommendations cover basic requirements pre-surgery, selecting the most appropriate anaesthetic and analgesic regimen, as well as intraoperative and post-operative care. The aim is to provide support for researchers and animal care staff to refine their procedures and practices, and implement small incremental changes to improve the welfare of the animals used and to answer the scientific question under investigation. All recommendations are recapitulated in a summary poster (see supplementary information)

Automated recording of home cage activity and temperature of individual rats housed in social groups: The Rodent Big Brother project

Measuring the activity and temperature of rats is commonly required in biomedical research. Conventional approaches necessitate single housing, which affects their behavior and wellbeing. We have used a subcutaneous radiofrequency identification (RFID) transponder to measure ambulatory activity and temperature of individual rats when group-housed in conventional, rack-mounted home cages. The transponder location and temperature is detected by a matrix of antennae in a baseplate under the cage. An infrared high-definition camera acquires side-view video of the cage and also enables automated detection of vertical activity. Validation studies showed that baseplate-derived ambulatory activity correlated well with manual tracking and with side-view whole-cage video pixel movement. This technology enables individual behavioral and temperature data to be acquired continuously from group-housed rats in their familiar, home cage environment. We demonstrate its ability to reliably detect naturally occurring behavioral effects, extending beyond the capabilities of routine observational tests and conventional monitoring equipment. It has numerous potential applications including safety pharmacology, toxicology, circadian biology, disease models and drug discovery

Real-time electrochemical monitoring of brain tissue oxygen: A surrogate for functional magnetic resonance imaging in rodents

Long-term in-vivo electrochemistry (LIVE) enables real-time monitoring and measurement of brain metabolites. In this study we have simultaneously obtained blood oxygenation level dependent (BOLD) fMRI and amperometric tissue O2 data from rat cerebral cortex, during both increases and decreases in inspired O2 content. BOLD and tissue O2 measurements demonstrated close correlation (r=0.7898) during complete (0%) O2 removal, with marked negative responses occurring ca. 30 s after the onset of O2 removal. Conversely, when the inspired O2 was increased (50, 70 and 100% O2 for 1 min) similar positive rapid changes (ca. 15 s) in both the BOLD and tissue O2 signals were observed. These findings demonstrate, for the first time, the practical feasibility of obtaining real-time metabolite information during fMRI acquisition, and that tissue O2 concentration monitored using an O2 sensor can serve as an index of changes in the magnitude of the BOLD response. As LIVE O2 sensors can be used in awake animals performing specific behavioural tasks the technique provides a viable animal surrogate of human fMRI experimentation

Real-time electrochemical monitoring of brain tissue oxygen: A surrogate for functional magnetic resonance imaging in rodents

Long-term in-vivo electrochemistry (LIVE) enables real-time monitoring and measurement of brain metabolites. In this study we have simultaneously obtained blood oxygenation level dependent (BOLD) fMRI and amperometric tissue O2 data from rat cerebral cortex, during both increases and decreases in inspired O2 content. BOLD and tissue O2 measurements demonstrated close correlation (r=0.7898) during complete (0%) O2 removal, with marked negative responses occurring ca. 30 s after the onset of O2 removal. Conversely, when the inspired O2 was increased (50, 70 and 100% O2 for 1 min) similar positive rapid changes (ca. 15 s) in both the BOLD and tissue O2 signals were observed. These findings demonstrate, for the first time, the practical feasibility of obtaining real-time metabolite information during fMRI acquisition, and that tissue O2 concentration monitored using an O2 sensor can serve as an index of changes in the magnitude of the BOLD response. As LIVE O2 sensors can be used in awake animals performing specific behavioural tasks the technique provides a viable animal surrogate of human fMRI experimentation