Introduction

Heating pads are extensively used for thermoregulation before, after, and amidst rodent surgeries. The ambient temperatures (20-24oC) of laboratories and vivariums where rodents are housed can cause hypothermia in the animals. Moreover, rodents are also prone to cold stress due to anesthesia and while recovering from anesthesia. Heating pads create thermoneutral environments in the cages, during and after surgery, preventing inadvertent hypothermia. 

The use of anesthetics for sedating animals during surgery interferes with normal temperature regulation mechanisms of the body. Exposure of skin to drugs and injection of large volumes of intravenous and irrigation fluids can result in significant loss of body heat, ultimately causing perioperative and postoperative hypothermia. This hypothermia is the leading cause of mortality in rodents due to their “high surface area to body mass ratio.” Therefore, the animal is provided with warmth via a heating pad during experiments to save them from cold stress.

In a general stereotaxic surgery (such as for implanting a probe or cannula in rodents’ brains), the heating pad is pre-warmed for 30 minutes before use. The rodents are then anesthetized using an intraperitoneal or respiratory drug. The animal is placed on a stereotaxic instrument, and loss of reflex is confirmed by toe pinching. The heating pad is then placed beneath the animal with a towel on the top to avoid thermal burns. The surgery is performed and the animal is shifted to the recovery cage. The heating pad is then placed underneath the recovery cage to prevent postoperative hypothermia. The duration for which a heating pad is used depends on the effect of the anesthetic/drug used. The heating pad should be warm enough not to let the temperature drop by 37oC. However, in hyperthermia (where the temperature exceeds 38oC), one must turn the heating pad off. 

Apparatus and Equipment

Conduct Science’s heating pad is made of non-toxic silicone. It offers temperature control between 25 and 45oC with a resolution of 0.1 degree Celsius. The heating pad is a part of the Homeothermic Monitoring System designed for optimal performance before, during, and after surgery. It can adapt well to multiple experimental platforms and is easy to use. You need to connect it to the Temperature Controller. It is available in three different sizes: rat, mouse, and cage, and is compatible with various stereotaxic instruments. The experimenter can easily clean the apparatus after use. 

Applications

Maintenance of Normothermic conditions during Dexmedetomidine administration 

Lavon et al. (2017) studied the effect of the drug Dexmedetomidine on metastasis in rodent models of breast, lung, and colon cancers. However, this drug is reported to cause potential hypothermia in rodent models. The animal can face cold stress for up to 8 hours after Dexmedetomidine administration. The researchers used heating pads (temperature adjusted at 40oC) for about 8 hours to resolve this problem. The hypothermic effects of the drug were easily overcome by the heating pad that induced normothermic conditions in the subject. They injected the subjects with the drug of choice, studied its effects, and concluded that dexmedetomidine increases metastasis and tumor cell retention in mammary and colon adenocarcinoma.

Prevention of Hypothermia in Stereotaxic Surgeries

Poole et al. (2019) anesthetized the animals for stereotaxic surgery to implant guide cannulas in rodent brains for administering drugs to the targeted regions and used a heating pad for thermoregulation. They took 28 to 30 days old postnatal male Sprague-Dawley rats weighing up to 120g housed in normal cages and shifted them into an induction chamber filled with 0.5% isoflurane. The isoflurane percentage was increased by 0.5% every 20 seconds until it reached 3.5%. The animals were allowed to inhale 3.5% isoflurane for approximately 3 minutes to get anesthetized. The animal was fixed into the stereotaxic frame. To prevent hypothermia, they placed the animal on a heating pad. A towel was placed as a barrier to avoid the animal’s direct contact with the heating pad. The lack of sensation was confirmed by ‘the pinch withdrawal reflex. They decreased the isoflurane concentration to 3% and then used a lubricated rectal thermometer for a temperature check. Researchers also ensured that the heating pad did not let the temperature drop below 37oC and increase above 37.5oC. They shaved the skin of the animal; the skull was incised and open for full exposure. And then removed pericranial tissues via cotton swabs, and the cannula was mounted on the bregma. In a nutshell, the researchers successfully implanted the cannulas with an overall mortality rate of 0%.  

Heating Pad’s Efficiency Assessment

Zhang et al. (2017) assessed the efficiency of the heating pad after Isoflurane administration in Sprague-Dawley rats. They aimed to ascertain an effective ‘warming period’ for maintaining normothermia during recovery. The researchers took eight male and nine female rats free from any bacterial or viral infection, habituated in polycarbonate cages in the form of pairs in a controlled housing environment (22% humidity, 23oC temperature, and 12:12h light and dark reactions). The animals were provided with food and water ad libitum. They pre-warmed the heating pad for 30 minutes and assessed its performance by measuring the temperature at different points on its surface. The rats were also acclimated to the recovery cages before testing, where they were handled for 15 minutes by the experimenter and presented with a reward. The animals were exposed to 5% isoflurane for 40 minutes until the loss of reflex and then shifted into the recovery cages. They were placed into two treatment groups: a) 30 minutes warming post-recovery and b) 60 minutes warming post-recovery. Experimenters measured the rectal and cage floor temperatures every 10 minutes, and the time spent in the recovery cage was 2 hours for each group.  This duration for the first group was divided into “30 min in the recovery cage and 90 min in the home cage”. For the second group, this time was divided into “60 min in the recovery cage and 60 min in the home cage”. They concluded that 60 minutes is an effective warming period for preventing rodents from hypothermia while recovering from general anesthesia.

Strengths and Limitations

The heating pads are easy to use and cost-effective. They can be adjusted according to the experimental setup and can be easily cleaned after use. They efficiently prevent rodents from hypothermia before, during, and after surgeries. However, direct contact of the heating pad with the rodents can cause thermal burns. The heating pads are placed partially under the cage such that only 50% of the cage is above the heating pad to avoid this issue. Also, an insulator like a towel is placed over the heating pad to avoid direct contact with the subject. 

Summary

• Heating pads are extensively used for thermoregulation before, after, and amidst rodent surgeries.
• Heating pads prevent pre-operative, postoperative, and perioperative hypothermia.
•  The heating pad should be warm enough not to let the temperature drop by 37oC. However, in hyperthermia (where the temperature exceeds 38oC), the heating pad is turned off. 
• Overheating of the pad can result in thermal burns.

References

1. Lavon, H., Matzner, P., Benbenishty, A., Sorski, L., Rossene, E., Haldar, R., Elbaz, E., Cata, J. P., Gottumukkala, V., & Ben-Eliyahu, S. (2018). Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancers. British journal of anesthesia, 120(1), 188-196.
2. Zhang, E. Q., Knight, C. G., & Pang, D. S. (2017). Heating pad performance and efficacy of 2 durations of warming after isoflurane anesthesia of Sprague–Dawley rats (Rattus Norvegicus).  Journal of the American Association for Laboratory Animal Science, 56(6), 786-791.
3. Poole, E. I., McGavin, J. J., Cochkanoff, N. L., & Crosby, K. M. (2019). Stereotaxic surgery for implantation of guide cannulas for microinjection into the dorsomedial hypothalamus in young rats. MethodsX, 6, 1652-1659.
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