The ability to accurately and non-invasively measure microcirculation systolic and diastolic blood pressure, as well as heart rate and other parameters of blood flow in rodents, is of great clinical value to the researcher.
Invasive Blood Pressure and Measurement of Rat and Mouse
Direct blood pressure, an invasive surgical procedure, is the gold standard for comparing the accuracy of non-invasive blood pressure (NIBP) techniques. Direct blood pressure should be obtained on the carotid artery of a rodent compared to NIBP. “Validation of awake rats for the tail-cuff method for systolic pressure measurement”, Bonagh, R.D., Journal of Applied Physiology, Volume 34, Pages 279-282, 1973.
Radio telemetry, a highly invasive surgical procedure, is a very reliable blood pressure technique and is also used to compare the accuracy of NIBP techniques. Telemetry involves implanting radio transmitters into a rodent’s body. This technique has been well validated and has an excellent correlation with direct blood pressure.
An advantage of implantable radiometry is the ability to continuously measure blood pressure in rats and mice in freely moving test animals.
The disadvantages of telemetry are: (1) the morbidity associated with the initial surgical implantation of the transmitter; (2) incidence of disease associated with a process required to replace the battery with short life span; (3) Increased level of animal fatigue, especially mice, in relation to large and heavy transmitters (2004, ATLA, Fourth World Congress, Einstein, Billing, Singh, and Chen); (Iv) Abnormal behavior where the animal cannot interact socially due to current technology microcirculation which requires isolating the cultivated animal, one animal per cage; (5) Inability to perform high-throughput sifting; (Vi) High initial installation costs of expensive equipment and transmitters requiring regular plant maintenance; (7) Material and human resource costs related to ongoing operations. And (8) the lack of a competitive market, which led to high costs of products and services.
Non-invasive blood pressure measurement and measurement of rats and mice
The NIBP methodology consists of using a tail band that is placed over the tail to cut off blood flow. During shrinkage, one of several types of NIBP sensors, located further away from the occlusion bracelet, may be used to monitor blood pressure in mice. There are three (3) types of NIBP sensor technologies: optical imaging, blood imaging, and volume pressure recording. Each method uses a clogging tail as part of the procedure.
1. Photography
The first and oldest type of sensor is optical imaging (PPG), which is a light-based technology. The purpose is to record the first appearance of the wrist during tire cuff contractions or the disappearance of impulses during a tire cuff enlargement. Photoplethysmography uses an incandescent lamp or LED light source to record the wave of a pulse signal. As such, the light-based plethysmography method uses a light source to illuminate a small spot on the tail and attempt to record the pulse.
Photogrammetry (PPG) is relatively imprecise because the measurements are based only on the amplitude of a single pulse and can only inaccurately measure systolic blood pressure and heart rate. There are several limitations to the light-based technology, such as (1).
Supersaturation of the BP signal with ambient light; (2) Extreme sensitivity to rodent movement (motion artifact); And (3) difficulty in obtaining adequate blood pressure signals in mice in dark-skinned rodents (pigmentation differentiation). The light-dependent sensors also cause tail burns from close contact and prolonged exposure.
Diastolic blood pressure cannot be measured with optical imaging because the technology only records the first occurrence of a pulse. When diastolic blood pressure is displayed on optical imaging tools, it is only an estimate calculated by a software algorithm and not an actual measurement.
Additional contrast and inaccuracy occur with PPG devices that rely on measurements while the occlusive bracelet inflates.
Clogging bracelet length is also another source of variability and inaccuracy. Obstructive cuff length is inversely related to blood pressure accuracy. Long cuffs, especially on most optical imaging devices, record less than actual blood pressure readings.
2. Blood mapping
The second NIBP sensor technology is piezoplethysmography. Combined granulomatosis and photodynamics require the same first occurrence of a pulse in the tail to record systolic blood pressure and heart rate.
Both plethysmographic methods have similar clinical limitations. While optical imaging uses a light source to try to record the pulse signal, electromyography uses piezoelectric ceramic crystals to do the same. From a technical point of view, granulomatosis is more sensitive to microcirculation than optical imaging, as the signal from the sensor is the rate of change of the pulse and not just the pulse amplitude. Therefore, even very small mice with a high-speed pulse will generate enough signal to be detected with simple amplifiers.
Piezoelectric sensors are more accurate than light / LED-based sensors, but the same limitations of plethysmography continue to cause inaccuracies in blood pressure measurements. On the plus side, rodents’ skin pigmentation is not a measurement problem in granulocytopenia as it is in photogrammetry.
While EMG is preferable to optical imaging, both non-invasive tail-cuff blood pressure techniques correlate poorly with direct blood pressure measurements.
3. Volume compression recording
The third sensor technology is Volume Pressure Recording (VPR). The volume pressure recording sensor uses a specially designed differential pressure transducer to measure blood volume in the tail without surgical intervention. Volume pressure recording basically measures six (6) parameters of blood pressure simultaneously: systolic, diastolic, median, heart rate, tail blood volume, and tail blood flow.
Since the volume pressure recording uses a volumetric method to measure blood flow and blood volume in the tail, there are no measuring instruments related to ambient light; The movement effect is also greatly reduced. In addition, the recording of volume pressure does microcirculation not depend on the color of the animal’s skin. Dark-skinned animals had no negative effect on sound recording pressure measurements. Very small 10 g black C57 / BL6 mice can be easily measured by the volume pressure recording method.
Special attention is paid to the length of the obstructed cuff to the volume pressure sensor to obtain the most accurate blood pressure readings.
Volume pressure recording is the most reliable, stable, and accurate method for non-invasive blood pressure measurement in mice as small as 10 g and mice larger than 950 g.
In an independent clinical investigation study conducted in 2003 at Yale University, New Haven, Connecticut, a volume pressure recording of 99 percent was linked to direct blood pressure:
“Volume pressure recording is excellent. It is very accurate and reliable. We have conducted experiments with temperature-controlled adult mice and non-invasive blood pressure measurements have shown an almost perfect correlation with invasive blood pressure measurements. We are very pleased with the results.”
Several published research papers are available to verify the accuracy, reliability, and consistency of volume pressure recording. See section Clinical Bibliography.
Keepers of rodents, mice, and mice
The ideal animal keeper should restrain the animal comfortably, create a low-pressure environment and allow the researcher to continuously monitor the animal’s behavior. A mouse or trained mouse can stay comfortable and relaxed in the carrier for several hours.
It is very helpful to include a dark nose cone in the rodent holder to restrict the animal’s vision and reduce the animal’s stress. The animal’s nose protrudes from the front of the nose cone allowing it to breathe comfortably. The animal’s tail should extend completely out and exit the hatch of the back door of the container.
The correct size animal guard is essential to measure blood pressure well. If the container is too small for the animal, the limited side space will not allow the microcirculation animal to breathe comfortably. The animal will compensate by lengthening its body, creating a respiratory artifact. The respiratory device causes excessive tail movement and unwanted blood pressure readings.
The body temperature of the animal, mice, and mouse
The NIBP system should be designed to comfortably warm the animal, reduce animal fatigue, and improve blood flow to the tail.
Rodents’ body temperature is very important for accurate and consistent blood pressure measurements. The animal must have sufficient blood flow in the tail to receive the blood pressure signal. Thermoregulation is the way an animal lowers its body temperature, dissipates heat through its tail, and generates blood flow in the tail.
