Avoiding Cold Stress in the Vivarium
Sponsored by:Presented by: Avoiding Cold Stress in the Vivarium Heated IVCs Allow Both Researchers and Animals to Remain in the Thermal Neutral Zone Avoiding Cold Stress in the Vivarium 2 Avoiding Cold Stress in the Vivarium Heated IVCs Allow Both Researchers and Animals to Remain in the Thermal Neutral Zone To guarantee consistent and reliable research, it is important that laboratory animals are housed appropriately and comfortably. Recent studies have indicated that laboratory mice and rats are currently kept at temperatures that are too cold, which can skew study results. However, for many facilities, the decision to keep the temperatures down comes down to worker comfort, resulting in cooler animal rooms. ALN Magazine spoke to Michael Metze, the Product Application Advisor at Alternative Design Manufacturing & Supply, about cold stress, thermal neutral zones, and their new heated IVC, Solace Zone. Solace Zone is a patent-pending technology that creates a thermal neutral zone within IVC to help alleviate cold stress in rodents. Solace Zone is currently available as a stand-alone product in a 32-cage mobile P.I. unit. What is cold stress? All warm-blooded animals have a Thermal Neutral Zone (TNZ). The Thermoneutral Zone is a range of temperatures of the immediate environment in which a standard healthy adult animal can maintain a normal body temperature without needing to use energy above and beyond normal basal metabolic rate. Cold stress is the body’s reaction to temperatures below the TNZ When the temperature decreases, the metabolic rate increases causing thermogenesis to increase the body temperature. The TNZ for mice is 79-93° F (26-34° C). The eighth edition of the NIH Guide for the Care and Use of Laboratory Animals (National Academies Press, 2011) recommends housing rodents in a micro-environment (cage) below the TNZ at 68-79° F (20-26° C), which can result in changes to their physiology and behavior. It has been documented in numerous studies that these changes in physiology can alter scientific outcomes, which have serious implications for animals meant to model human biological systems. How does temperature variation affect research results and why it is important to recognize? Studies conducted at the University of California, Los Angeles (UCLA) show chronic cold stress in rodents housed at the temperatures recommended in the Guide for the Care and Use of Laboratory Animals. This chronic cold stress causes greater energy expenditure and high glucose utilization. Here’s an excerpt from a 2013 study published in Comparative Medicine on this subject: The Hidden Cost of Housing Practices: Using Noninvasive Imaging to Quantify the Metabolic Demands of Chronic Cold Stress of Laboratory Mice John M David, Arion F Chatziioannou, Richard Taschereau, Hongkai Wang, and David B Stout, University of California, Los Angeles Systemic physiologic cold stress creates a much greater energy demand on mice than humans due to the surface area to volume ratio. Mice housed at routine vivarium temperatures have greater oxygen consumption and feed intake than at thermoneutral temperatures (86°F/30°C). Ultimately, this difference may adversely affect translational research, sometimes in unpredictable ways. For example, mice housed at temperatures below their thermoneutral zone have a blunted response to lipopolysacharide-induced fever and lack the classic early-phase hypothermia, demonstrating impaired immune function. In another example, blood pressure and heart rate are significantly elevated at routine vivar- ium temperatures compared with thermoneutral temperatures, again demonstrat- ing that rodent physiology is perturbed under such housing conditions. The research results as conducted within the cold stress environment cannot be considered as “normal” and hence the data extrapolation to the human may have serious consequences. How does a thermal neutral zone improve laboratory animal welfare? Foremost, the animals are comfortable and metabolically stable. They have greater immune response. They become behaviorally more compatible. For more on this subject, here’s an excerpt from a 2012 study published in the Journal of Experimental Medicine: Unstressing Intemperate Models: How Cold Stress Undermines Mouse Modeling Christopher L. Karp, Cincinnati Children’s Research Foundation For reasons of human comfort and historical contingency, mice are systematically housed at temperatures comfortable for clothed humans, i.e., “room tempera- ture,” which is 66-71° F (19-22° C). However, the thermoneutral zone for most mouse strains (during the day when they are inactive) is 86-90 °F (30-32 °C) (Gordon, 1993). Mice are thus normally subjected to cold stress, the extent of which is illustrated by the dramatic decrease in heart rate (200 beats/min from 550-600 to 350-400 beats/min) observed when mice are shifted from such temperatures to thermoneutrality (Swoap et al., 2008). Paralleling this, the “basal” metabolic rate of mice housed under standard conditions is elevated by 50-60% compared with that of mice housed at thermoneutrality. Avoiding Cold Stress in the Vivarium 3 Avoiding Cold Stress in the Vivarium 4 Infection, Immunity, and Thermoneutrality Studies dating back at least to the 1940s indicate that ambient temperature profoundly alters the course of infection in diverse rodent models. In models of bacterial (Salmonella typhimurium, Staphylococcus aureus, Klebsiella pneumonia, and Rickettsia typhi), viral (influenza virus, herpes simplex virus, and rabies virus), and protozoal (Trypanosoma cruzi) infection, ambient temperature directly correlates with host responsiveness—lower temperatures leading to impaired immune responses. Behavior Finally, it should be noted that these issues have important implications for the study of behavior as well. Social isolation is a commonly used stressor in murine behavioral research. As solitary mice cannot huddle for warmth, such isolation increases the cold stress associated with standard housing, thus introducing an important confounding variable. More broadly, our own experience in setting up a vivarium room to house mice at thermoneutrality has made it clear that ambient temperature has a profound effect on mouse behavior—the aggressive nippiness of male C57BL/6 mice evaporates under such conditions. How does a thermal neutral zone affect the welfare of the people in the laboratory? Adjusting the animal room temperature to the thermoneutral zone of mice will cause the researchers and animal care staff to go into “heat stress” and possibly even heat exhaustion! The temperature increase of the room along with the required PPE (Personal Protective Equipment) such as coveralls/gown, cap, gloves, and mask will make it impossible to work in the room for any length of time. What makes the Solace Zone unique in the market? At the present time, Solace Zone is the only heated IVC available in the lab animal research industry. What types of facilities would benefit from use of Solace Zone? Any facility that is involved in mouse research would benefit greatly from having a heated IVC unit at their disposal to remove the potential impact of cold stress on their research results. Solace Zone also works great in the recovery of surgical animals. Avoiding Cold Stress in the Vivarium 5 Can I customize Solace Zone to meet my facility’s unique needs? Currently, the patent-pending technology used in the Solace Zone unit is only available in the current 32-cage mobile P.I. unit configuration. Alternative Design is in the process of determining how this technology might be utilized with additional lab equipment and animal species (i.e., rats) in the future. How can I learn more about Solace Zone? Anyone interested in learning more about the features and benefits of the Solace Zone heated IVC unit can either visit the special Solace Zone page of Alternative Design’s website (www.altdesign.com/solacezone) or contact the representative for your area (www.altdesign.com/contact-us/contact-sales).