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Avoiding Cold Stress

in the Vivarium
Heated IVCs Allow Both Researchers and
Animals to Remain in the Thermal Neutral Zone

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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 bodys 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. Heres an excerpt from a 2013 study published in Comparative
Medicine on this subject:

Avoiding Cold Stress in the Vivarium

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 (86F/30C). 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 vivarium temperatures compared with thermoneutral temperatures, again demonstrating 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,
heres 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 Childrens Research Foundation
For reasons of human comfort and historical contingency, mice are systematically
housed at temperatures comfortable for clothed humans, i.e., room temperature, 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

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 responsivenesslower 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
behaviorthe 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

Can I customize Solace Zone to meet my facilitys


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 Designs
website (www.altdesign.com/solacezone) or contact the representative for your area
(www.altdesign.com/contact-us/contact-sales).

Avoiding Cold Stress in the Vivarium