The ability to evaluate distress in laboratory animals is needed in order to ensure that husbandry and experimental procedures do not negatively impact animal welfare. Accurate measurement of acute stress and chronic stress, and distinguishing between stress that is harmful (distress) and stress that does no harm (eustress), can be challenging. Whereas corticosterone concentrations are commonly used to measure stress in laboratory animals, the neutrophil-lymphocyte ratio has been proposed as a potentially better indicator of chronic stress. Furthermore, an association between such measures of stress and concurrent behavioral indicators of negative welfare is required to determine their accuracy in evaluating distress. The authors compared serum corticosterone concentrations and neutrophil-lymphocyte ratios to assess acute or chronic stress in male Sprague Dawley rats. Elevated serum corticosterone concentrations, but not neutrophil-lymphocyte ratios, were associated with acute stress exposure, whereas elevated neutrophil-lymphocyte ratios, but not serum corticosterone concentrations, were associated with chronic stress exposure. Because the neutrophil-lymphocyte ratio differences corresponded with a behavioral indicator of distress in chronically stressed rats, it may serve as a valuable tool for the physiological assessment of distress in rats.
Simple SummaryCurrent recommendations for the use of CO2 as a euthanasia agent for rats require the use of gradual fill methods in order to render the animal insensible prior to their experience of pain. However, there is concern that the use of these gradual fill methods may increase the distress experienced by these animals. We evaluated social and anxiety behavior of rats that had been exposed to concentrations of CO2 that did not cause a loss of consciousness. We also evaluated the physiologic changes of rats that were euthanized with gradual fill protocols as compared to rapid fill methods. We found that rats exposed to concentrations of CO2 that did not cause a loss of consciousness did exhibit increased anxiety and decreased social behavior. We also found that the use of a 10% volume per minute displacement rate of CO2 resulted in physiologic and behavioral changes suggestive of distress.AbstractCurrent recommendations for the use of CO2 as a euthanasia agent for rats require the use of gradual fill protocols (such as 10% to 30% volume displacement per minute) in order to render the animal insensible prior to exposure to levels of CO2 that are associated with pain. However, exposing rats to CO2, concentrations as low as 7% CO2 are reported to cause distress and 10%–20% CO2 induces panic-associated behavior and physiology, but loss of consciousness does not occur until CO2 concentrations are at least 40%. This suggests that the use of the currently recommended low flow volume per minute displacement rates create a situation where rats are exposed to concentrations of CO2 that induce anxiety, panic, and distress for prolonged periods of time. This study first characterized the response of male rats exposed to normoxic 20% CO2 for a prolonged period of time as compared to room air controls. It demonstrated that rats exposed to this experimental condition displayed clinical signs consistent with significantly increased panic-associated behavior and physiology during CO2 exposure. When atmospheric air was then again delivered, there was a robust increase in respiration rate that coincided with rats moving to the air intake. The rats exposed to CO2 also displayed behaviors consistent with increased anxiety in the behavioral testing that followed the exposure. Next, this study assessed the behavioral and physiologic responses of rats that were euthanized with 100% CO2 infused at 10%, 30%, or 100% volume per minute displacement rates. Analysis of the concentrations of CO2 and oxygen in the euthanasia chamber and the behavioral responses of the rats suggest that the use of the very low flow volume per minute displacement rate (10%) may prolong the duration of panicogenic ranges of ambient CO2, while the use of the higher flow volume per minute displacement rate (100%) increases agitation. Therefore, of the volume displacement per minute rates evaluated, this study suggests that 30% minimizes the potential pain and distress experienced by the animal.
Key Points
Question
Is the Johns Hopkins Community Health Partnership, a broad care coordination program inclusive of acute care and community interventions, associated with improved health outcomes?
Findings
This quality improvement study found that the community intervention was associated with a statistically significant reduction in admissions, readmissions, and emergency department visits for Medicaid, but the utilization results were mixed for the acute care intervention. In terms of cost of care, there were statistically significant cost savings totaling $113.3 million.
Meaning
A care coordination model in an urban academic center environment can be associated with improved outcomes, including substantial cost reduction.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.