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Non-Invasive Blood Pressure in Mice and Rats
Over the past 20 years, research scientists have attempted to non-invasively measure the blood pressure in mice and rats with varying degrees of success. The ability to accurately and non-invasively measure the systolic and diastolic blood pressure, in addition to the heart pulse rate and other blood flow parameters in rodents, is of great clinical value to the researcher. Additional recommended knowledge
Invasive Blood PressureDirect blood pressure, an invasive surgical procedure, is the gold standard to compare the accuracy of non-invasive blood pressure technologies. Direct blood pressure should be obtained on the rodent’s carotid artery when comparing to non-invasive blood pressure. “Validation in Awake Rats of a Tail Cuff Method for Measuring Systolic Pressure”, Bunag, R.D., Journal of Applied Physiology, Vol 34, Pgs 279-282, 1973. Radiotelemetry, a highly invasive surgical procedure, is a very reliable blood pressure technology and is also utilized to compare the accuracy of non-invasive blood pressure technologies. Telemetry involves the implantation of radio transmitters in the rodent’s body. This technique is well validated and has excellent correlation with direct blood pressure. The advantage of implantable radio telemetry is the ability to continuously measure blood pressure in free moving laboratory animals. The disadvantages of radiotelemetry are: (1) morbidity associated with the initial surgical implantation of the transmitter; (2) morbidity associated with surgery required to replace the battery, which has a short battery life; (3) increase in the animal’s level of stress, especially mice, in relationship to the large, heavy transmitters (2004, ATLA, 4th World Congress, Einstein, Billing, Singh and Chin); (4) abnormal behavior since the animal cannot have social interaction due to the current technology requiring the implanted animal to be isolated, one animal per cage; (5) inability to perform high throughput screening; (6) high cost of the initial equipment set-up and the expensive transmitters that require frequent factory maintenance; (7) cost of material and human resources relating to ongoing surgeries; and (8) the lack of a competitive market resulting in high product and servicing costs. Non-Invasive Blood PressureThe non-invasive blood pressure methodology consists of utilizing a tail-cuff placed on the tail to occlude the blood flow. Upon deflation, one of several types of non-invasive blood pressure sensors, placed distal to the occlusion cuff, can be utilized to monitor the blood pressure. There are three (3) types of non-invasive blood pressure sensor technologies: photoplethysmography, piezoplethysmography and Volume Pressure Recording. Each method will utilize an occlusion tail-cuff as part of the procedure. 1. Photoplethysmography
2. Piezoplethysmography
3. Volume Pressure Recording
Rodent HoldersThe ideal animal holder should comfortably restrain the animal, create a low-stress environment and allow the researcher to constantly observe the animal’s behavior. A trained rat or mouse can comfortably and quietly remain in the holder for several hours. It is very beneficial to incorporate a darkened nose cone into the rodent holder to limit the animal’s view and reduce the level of animal stress. The animal’s nose will protrude through the front of the nose cone allowing for comfortable breathing. The tail of the animal should be fully extended and exit through the rear hatch opening of the holder. The proper size animal holder is essential for proper blood pressure measurements. If the holder is too small for the animal, the limited lateral space will not allow the animal to breathe in a relaxed fashion. The animal will compensate by elongating its body, thereby creating a breathing artifact. A breathing artifact will cause excessive tail motion and undesirable blood pressure readings. Animal Body TemperatureA non-invasive blood pressure system should be designed to comfortably warm the animal, reduce the animal’s stress and enhance blood flow to the tail. The rodent’s core body temperature is very important for accurate and consistent blood pressure measurements. The animal must have adequate blood flow in the tail to acquire a blood pressure signal. Thermo-regulation is the method by which the animal reduces its core body temperature, dissipates heat through its tail and generates tail blood flow. Anesthetized animals may have a lower body temperature than awake animals so additional care must be administered to maintain the animal’s proper core body temperature. An infrared warming blanket or a re-circulating water pump with a warm water blanket is the preferred method to maintain the animal’s proper core body temperature. The animal should be warm and comfortable but never hot. Extreme care must be exercised to never overheat the animal. Warming devices such as hot air heating chambers, heat lamps or heating platforms that apply direct heat to the animal’s feet are not advisable to maintain the animal’s core body temperature. These heating devices will overheat the animal and increase the animal’s respiratory rate, thereby increasing the animal’s stress level. These conditions will elicit poor thermo-regulatory responses and create inconsistent and inaccurate blood pressure readings. Environmental TemperatureThe proper room temperature is essential for accurate blood pressure measurements. The room temperature should be at or above 26°C. If the room temperature is too cool, such as below 22°C, the animal will not thermo-regulate, tail blood flow will be reduced and it may be difficult to obtain blood pressure signals. A cold steel table or a nearby air conditioning duct are undesirable during animal testing. Animal PreparationThe animal should be placed in the holder at least 10 to 15 minutes prior to obtaining pressure measurements. Acclimated animals will provide faster BP measurements than non-acclimated animals. Proper animal handling is critical to consistent and accurate blood pressure measurements. A nervous, stressed animal may have diminished circulation in the tail. Most rodents will quickly adapt to new conditions and feel comfortable in small, dark and confined spaces. Training is not necessary to obtain accurate blood pressure readings, however, some researchers prefer training sessions. Rodents can easily be trained in approximately three days, 15-minutes each day before beginning your experiment. The animal should be allowed to enter the holder freely. After the animal is in the holder, adjust the nose cone so the animal is comfortable but not able to move excessively. The animal should never have its head bent sideways or its body compressed against the back hatch. The animal’s temperature should be monitored throughout the experiment. ConclusionTail-cuff non-invasive blood pressure measurements can be consistent, accurate and reproducible when studying awake and anesthetized mice and rats. In addition, multiple animal testing is very cost-effective for large scale, high throughput screening. Care must be exercised to properly handle the animals. Training the animals and monitoring the animal’s temperature may also be beneficial. The volumetric pressure recording method provides the highest degree of correlation with telemetry and direct blood pressure and is clearly the preferred tail-cuff sensor technology. Non-invasive blood pressure devices that utilize Volume Pressure Recording are a valuable tool in research and will continue to be beneficial in many study protocols. The main advantages are: (1) they require no surgery; (2) they are significantly less expensive than other blood pressure equipment, such as telemetry; (3) they can screen for systolic and diastolic BP changes over time in large numbers of animals; and (4) they provide the researcher with the ability to obtain accurate and consistent blood pressure measurements over time in long-term studies. Article published in Animal Lab News, November/December 2005 issue, click here to view. References
Categories: Medical research | Physiology |
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This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Non-Invasive_Blood_Pressure_in_Mice_and_Rats". A list of authors is available in Wikipedia. |