Experimental and husbandry procedures as potential modifiers of the results of phenotyping tests

To maximize the sensitivity of detecting affects of genetic variants in mice, variables have been minimized through the use of inbred mouse lines, by eliminating infectious organisms and controlling environmental variables. However, the impact of standard animal husbandry and experimental procedures on the validity of experimental data is under appreciated. In this study we monitored the impact of these procedures by using parameters that reflect stress and physiological responses to it. Short-term measures included telemetered heart rate and systolic arterial pressure, core body temperature and blood glucose, while longer-term parameters were assessed such as body weight. Male and female C57BL6/NTac mice were subjected to a range of stressors with different perceived severities ranging from repeated blood glucose and core temperature measurement procedures, intra-peritoneal injection and overnight fasting to cage transport and cage changing.Our studies reveal that common husbandry and experimental procedures significantly influence mouse physiology and behaviour. Systolic arterial pressure, heart rate, locomotor activity, core temperature and blood glucose were elevated in response to a range of experimental procedures. Differences between sexes were evident, female mice displayed more sustained cardiovascular responses and locomotor activity than male mice. These results have important implications for the design and implementation of multiple component experiments where the lasting effects of stress from previous tests may modify the outcomes of subsequent ones.     

Novel long-term cardiovascular effects of industrial noise

Baboon subjects were instrumented with indwelling arterial catheters for continuous measurement of blood pressure and heart rate before, during, and after exposure to industrial noise eight hours daily. Initial exposure to noise produced transient, acute elevations of systolic and diastolic blood pressures and heart rates at noise onset, which habituated over the course of noise exposure. Chronic exposure to noise lowered blood pressure and heart rate not only during noise, but particularly after daily noise offset. Blood pressures returned toward baseline after noise exposure was terminated. Plasma catecholamines were also decreased during noise exposure. A control animal which received only masking noise did not demonstrate decreases in cardiovascular parameters. The possibility of classically conditioned associations of noise onset with feeding was discussed.     

Integrated circuit system for digitizing arterial blood pressure and heart rate

The measurement of arterial blood pressure during physiological, pharmacological or behavioral manipulations generates a vast amount of data which must be reduced. Hand scoring is both time consuming and inaccurate, while on-line computer analysis may be prohibitively expensive. As an alternative, an inexpensive circuit is described which digitizes, stores, and prints out mean systolic and diastolic blood pressure, as well as heart rate, from up to four analog channels. Channels are sequentially digitized, each for an interval dialed on the front panel (1–999 sec). For each beat, a peak and trough detector enables the systolic and diastolic accumulators, respectively, thus storing two ten bit words from the analog to digital converter. For each systolic occurrence, a count of one is added to the heart rate counter. At the end of the recording interval, an output routine prints the interval number, mean systolic pressure, mean diastolic pressure, and total heart beats. Offset and gain controls allow precise calibration of various transducer and polygraph amplifiers.     

Changes in blood pressure and heart rate following bilateral olfactory bulbectomy in rats

Changes in blood pressure and heart rate following bilateral olfactory bulb ablation were investigated in unanesthetized and unrestrained rats with chronic arterial cannula implants. After bilateral olfactory bulbectomy, the rat exhibited a marked increase of emotional responses to given stimuli and a high incidence of muricide. Blood pressure and heart rate at 5 and 10 days after olfactory bulbectomy were significantly lower than in intact rats (rats before bulbectomy) and/or sham operated rats. Marked decreases in blood pressure and heart rate were seen especially in the period when the animals showed exploratory behavior after being transferred to the experimental cage from the home cage. These results suggest that olfactory bulbectomy has a great influence not only on emotionality but also on the central regulatory system of blood pressure in the rat.     

Telemetric analysis of haemodynamic regulation during voluntary exercise training in mouse models

Regular physical exercise reduces the risk of cardiovascular disease and improves outcome in patients with cardiovascular diseases. The dynamic changes in blood pressure and heart rate with acute exercise are independently predictive of prognosis. Quantification of the haemodynamic response to exercise training in genetically modified mouse models may provide insight into the molecular mechanisms underlying the beneficial effects of exercise. We describe, for the first time, the use of radiotelemetry to provide continuous blood pressure monitoring in C57BL/6J mice during a programme of voluntary wheel exercise with continuous simultaneous recording and analysis of wheel rotations and beat-by-beat haemodynamic parameters. We define distinct haemodynamic profiles at rest, during normal cage activity and during episodes of voluntary wheel running. We show that whilst cage activity is associated with significant rises both in blood pressure and in heart rate, voluntary wheel running leads to a further substantial rise in heart rate with only a small increment in blood pressure. With 5 weeks of chronic exercise training, resting heart rate progressively falls, but heart rate during episodes of wheel running initially increases. In contrast, there are minimal changes in blood pressure in response to chronic exercise training. Finally, we have quantified the acute changes in heart rate at the onset of and recovery from individual episodes of wheel running, revealing that changes in heart rate are extremely rapid and that the peak rate of change of heart rate increases with chronic exercise training. The results of this study have important implications for the use of genetically modified mouse models to investigate the beneficial haemodynamic effects of chronic exercise on blood pressure and cardiovascular diseases.     

A simple device for the direct measurement of mean arterial pressure and for calibration of arterial pressure monitors

A simple, inexpensive mechanical device is described for the direct continuous measurement of mean arterial pressure. It can be assembled in minutes using a few dollars worth of sterile components commonly available in an intensive care unit. Mean arterial pressure determined in patients with this device differs by 1.6 mmHg +/- 1.1 SD from mean arterial pressure simultaneously measured by properly calibrated Hewlett-Packard electronic monitors (N = 5), a non-significant difference. Similar agreement was obtained when the device was tested using a commercial blood pressure system calibrator as the pressure source. This device also allows rapid static calibration of electronic pressure transducers across the full range of human blood pressure using a 3 ml syringe as the pressure source and an aneroid gauge, or mercury column, as the pressure standard.     

Cardiovascular reflex responses to cutaneous and visceral stimuli in spinal man

1. A study has been made of the effects of pinprick and a cold pack applied to the skin above and below the level of denervation, deep inspiration, squeezing the chest, and bladder percussion in non-bedridden patients with chronic, closed, complete, localized transection of the cervical spinal cord. Variables studied were blood pressure, heart rate, calf blood flow, hand blood flow and occluded vein pressure in the hand and foot.2. Cutaneous stimuli above the lesion, mental arithmetic and noise from gunshot produced no response.3. Pinprick and cold applied below the lesion usually produced an increase in mean arterial pressure, little change in pulse pressure or heart rate, clear decreases in calf and hand blood flow, and occasional venoconstriction.4. Deep inspiration produced an initial rise in blood pressure and heart rate which was sometimes followed by a decrease in one or both. Squeezing the chest usually produced an increase in blood pressure and a decrease in heart rate. Both stimuli caused decreases in calf and hand blood flow and venoconstriction, the latter being more common after squeezing the chest.5. Bladder percussion produced contraction of the wall of the bladder and this was regularly associated with increased arterial mean and pulse pressures, a decreased heart rate and calf and hand blood flow, and venoconstriction. The responses occurred whether or not the bladder was full and whether or not a rise of intravesical pressure occurred.     

Effects of posture,hypotension and locally applied vasoconstriction on the middle ear microcirculation in anaesthetized humans

Studies by laser-Doppler flowmetry of middle ear microcirculation changes induced by physical and chemical stimuli in the animal have only recently been made. This prospective study, performed in humans, was designed to compare the effects of a postural manoeuvre (headup tilt 30°), hypotension and locally applied vasoconstriction on middle ear blood flow during anaesthesia. Circulatory changes provoked by a headup tilt of 30°, and successive intravenous boluses of potent vasodilators, were compared with circulatory changes provoked by locally applied adrenaline, in ten healthy patients in good physical states undergoing middle ear surgical repair. Heart rate and direct arterial pressure were continuously recorded via a radial artery cannula. Middle ear blood flow was continuously recorded via a laser-Doppler probe placed on the promontorium cavi tympani. Metabolic parameters (partial pressure of O₂ and CO₂ in arterial blood, pH, arterial lactate concentrations) and arterial concentrations of propofol were measured just before and just after the experiment. Headup tilt did not modify heart rate, mean arterial pressure or middle ear blood flow. Vasodilators (nicardipine, nitroprusside, nitroglycerin) provoked a fall in arterial pressure (P<0.0001,P<0.0001,P<0.019, respectively), but did not induce any significant variations in heart rate; variations occurred in middle ear blood flow (P>0.05, not significant) which were different according to patients and agents. Locally applied adrenaline provoked a fall in the middle ear blood flow (P<0.0012), with no effect on heart rate and arterial pressure. There were no significant changes in metabolic values, or propofol serum concentrations. The behaviour of the middle ear blood flow submitted to hypotension, posture, or to vasoconstriction could be related to counteracting regulatory responses and/or to direct vascular effects.     

一种可监测人体脉搏波的汽车方向盘辅助装置

目的脉搏波的波形特征与心血管疾病密切相关。本文拟设计一种安装在汽车方向盘上的能独立实时监测脉搏波信号的辅助装置,在驾驶员无意识下获取其血流动力学的相关信息,为监测健康状况提供数据支持。方法该装置利用置于方向盘套表面的反射式脉搏波光电传感器采集脉搏波信号。经过滤波、放大和A／D转换,利用嵌于方向盘助力器内的配套装置对脉搏波信号进行数字处理,实现对脉搏波信号周期的确定、心率和平均动脉压数据的计算,以及信号和数据的存储。最后将处理后的脉搏波波形、心率数据及平均动脉压显示在配套装置的液晶显示屏上,还可通过配套装置中的SD卡接口进行数据传输及存储。结果经受试者实际测试,传感器能够准确测出手指脉搏波并输出,使得方向盘套和助力器具有测量脉搏波、心率及平均动脉压的功能。结论该汽车方向盘辅助器可为用户实时监测脉搏波、心率和平均动脉压,帮助使用者实时监测自己的健康状况。     

Ambulatory monitoring of indirect beat-to-beat arterial pressure in human fingers by a volume-compensation method

Using a volume-compensation technique, a portable device has been designed for the indirect measurement of beat-to-beat arterial pressure and its waveforms in the basal phalanx of fingers of ambulatory subjects. The device consists of (1) a transmission infra-red photoelectric plethysmograph (TIPP) to detect the variation of arterial volume, (2) a pneumatic cuff with an actuator, (3) a servosystem to control the cuff pressure, and (4) a stereo cassette tape recorder. Arterial pressure was determined from the cuff pressure which was controlled by the servosystem so as to maintain the arterial volume constant at the 'vascular unloading' state. This device is equipped with a compensator for any hydrostatic pressure difference between the heart and finger. Thus, the blood pressure at heart level can be obtained for any finger height. The total weight of the device was 1.6 kg. Blood pressure changes during walking, jogging, jumping, and exercises such as side-stepping, Master's two-step test and car driving, have been successfully recorded.     

Toward a portable blood pressure recorder device equipped with an accelerometer

The 24-h ambulatory systolic blood pressure (ASBP) recording has become a helpful tool in the diagnosis of hypertension and evaluation of the efficiency of anti-hypertensive drugs. Yet, the very high variability of ASBP makes the analysis of the recording rather difficult. A potential solution to reduce ASBP variability has been studied and is presented in this article. It consists of equipping the portable ASBP recorder device with other sensors, a three axes accelerometer and a heart rate recorder, so as to enable an analysis to be undertaken of the arterial pressure profile in the light of these concomitant data. A database has been collected, and a model linking ASBP variations with body acceleration and heart rate measurements is developed. Its performance is tested in prediction and the results compared with those obtained from one of the solutions currently used by physicians to deal with ASBP variability. The results obtained with 16 young subjects from the database, for whom two 24-h recordings are available, are significantly improved and very encouraging.     

Long-term ambulatory monitoring of indirect arterial blood pressure using a volume-oscillometric method

A new portable instrument equipped with a microprocessor was designed for the long-term ambulatory monitoring of indirect arterial pressure in the human finger at desired intervals using a volume-oscillometric technique. All the necessary procedures such as (1) programmed control of cuff pressure, (2) detection of the systolic end-point and the point of maximum amplitude of arterial volume pulsations, (3) reading of the cuff pressures corresponding to these two points, (4) its processing and (5) recording of the systolic and mean pressure together with heart rate on a digital memory integrated circuit were performed automatically. After the monitoring, the data were reproduced and analysed by a conventional personal computer. Simultaneous comparison of the data with direct measurement, operation and evaluation of this instrument, and ambulatory monitoring were carried out. With this instrument noninvasive and accurate monitoring of arterial pressure could be made in unrestricted subjects during daily activities.     

Computerized blood pressure and heart rate recording system interfaces standard chart recorder with any micro-computer.

The designed inexpensive blood pressure recording system (BPRS) gives any microcomputer direct on-line blood pressure and heart rate recording capability that will save research time and increase the accuracy of collected data. The data is automatically stored in a file compatible with most graphic and statistical processing software. In vitro testing, over a range of 0-200 mmHg and 0-360 beats per minute showed a 0.999 intraclass correlation. In vivo testing of the BPRS used anaesthetized rats whereby their systolic and diastolic pressures were measured simultaneously with heart rate. The blood pressures and heart rate data, measured by the BPRS demonstrated excellent stability, sensitivity and accuracy when compared to those measured by standard pressure transducers in conjunction with a Grass polygraph and a sphygmomanometer.     

Non-steady airflow measurement using pressure differential techniques

A method is presented for the direct measurement of small airflows in particular physiological situations, with especial reference to flow in the avian lung. The Pitot principle of flow-induced pressure differentials is incorporated into a non-linear device. Its properties, calibration and linearization are discussed. The general problem is considered of identification, explanation and practical reduction of artefacts incident upon the recording of low pressure differentials by means of air transmission cannula-manometer arrangements with a relatively high time-constant of response.     

Polyimide/SU-8 catheter-tip MEMS gauge pressure sensor

This paper describes the development of a polyimide/SU-8 catheter-tip MEMS gauge pressure sensor. Finite element analysis was used to investigate critical parameters, impacting on the device design and sensing characteristics. The sensing element of the device was fabricated by polyimide-based micromachining on a flexible membrane, using embedded thin-film metallic wires as piezoresistive elements. A chamber containing this flexible membrane was sealed using an adapted SU-8 bonding technique. The device was evaluated experimentally and its overall performance compared with a commercial silicon-based pressure sensor. Furthermore, the device use was demonstrated by measuring blood pressure and heart rate in vivo.     

基于电磁驱动的体外膜肺氧合搏动式泵血系统

根据电磁学原理建立梯度线圈-永磁体模型,本研究设计了一款新型电磁驱动搏动式血泵,主要包括驱动装置、泵头装置、冷却系统以及体外循环管路等.搏动式血泵运动速率接近正常人体心率,模仿心脏的节律跳动,产生搏动式血流,实现了搏动式泵血.通过搭建实验平台,采集基于电磁驱动的体外膜肺氧合(extracorporeal membran...     

Cardiovascular effects of central 6-OHDA treatment: a comparison of indirect and direct measurements

The effect of intracerebro-ventricular treatment with 6-hydroxydopamine on blood pressure and heart rate was studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto controls (WKY). When measured with the indirect tail-cuff method, the development of hypertension was found to be markedly inhibited in 6-OHDA treated SHR, while blood pressure was slightly lower in treated WKY. Heart rate was lower in both strains, although the greatest effect was found in SHR. In contrast, direct measurement via an arterial cannula indicated significantly lower blood pressure in 6-OHDA treated SHR only. Heart rate was by this method found to be not different between the SHR groups, but was increased in treated WKY. These results indicate that the mild stress of indirect blood pressure determinations has a marked influence on the results found.     

Signalling across the blood brain barrier by angiotensin II: novel implications for neurogenic hypertension

Angiotensin II (AngII) is a major culprit in essential hypertension. Based on a genetic rodent model of hypertension, we review here evidence that AngII may signal across the blood brain barrier to affect neuronal circuits within the nucleus tractus solitarii (NTS) of the brainstem, a pivotal region regulating both the baroreceptor reflex and set point control of arterial pressure. We have termed this form of signalling as vascular–neuronal signalling. We describe that the depressant action of AngII in NTS on the baroreceptor reflex is mediated via activation of endothelial nitric oxide synthase (eNOS) releasing NO that promotes release of the inhibitory transmitter—GABA. This could shunt the incoming excitatory baroreceptor afferent traffic impinging on NTS neurones. Chronic studies recording arterial pressure in conscious unrestrained rats using radio-telemetry have revealed that eNOS in NTS plays an endogenous physiological role in the homeostatic regulation of the gain of the cardiac baroreceptor reflex. However, in the spontaneously hypertensive rat, eNOS mRNA was higher (compared to normotensive rats), and its chronic blockade in NTS restored the abnormally depressed cardiac baroreceptor reflex to levels akin to normotensive rats, improved heart rate variability and lowered arterial pressure. Hence, it seems that excessive eNOS activity in NTS of the SHR contributes to the pathological state of this animal model’s cardiovascular autonomic nervous system. We speculate on why eNOS activity may be up regulated in the NTS of the SHR and propose that it is a consequence of high cerebral vascular resistance and inadequate blood perfusion of the brainstem.     

Measurement of Neonatal Blood Pressure: A New Method

Psychophysiological research on the neonatal cardiac system has focused almost exclusively on heart rate. Other cardiovascular parameters such as blood pressure (BP) have been difficult, if not impossible, to examine in the newborn due to the difficulty involved in measurement. This study tested a new, non-invasive device that simultaneously measured systolic, diastolic, and mean arterial BP and heart rate in the newborn. Eighty healthy babies’ BP and heart rate were measured for the first 3 days of life and the findings were compared with previous reports in the literature. BP was found to increase on each of the first 3 days of life while mean heart rate did not change during this period. State of alertness significantly affected BP and heart rate, with sucking leading to the greatest rise in BP, while crying elicited the highest heart rates. The results indicated that this new non-invasive technology provides an important advance that has considerable bearing on future studies of neonatal psychophysiology.     

Electrical admittance cuff for non-invasive and simultaneous measurement of haematocrit,arterial pressure and elasticity using volume-oscillometric method

An improved technique based on the electrical admittance cuff was designed for the non-invasive measurement of haematocrit (Hct), together with blood pressure (BP) and arterial elasticity represented as volume elastic modulus (E_v), in human fingers. This device is made of a rigid annular chamber installed with a surrounding thin-walled tube (cuff), which is filled with electrolyte solution. A tetrapolar method is used to detect the admittance signals, both in the solution and in a finger segment placed through the cuff. With this device, it is theoretically shown that the resistivity of blood flowing into the segment is equal to that of the solution multiplied by the ratio of the admittance variation in the solution to that in the segment. Thus, the blood resistivity and therefore Hct can be non-invasively determined from the electrolyte resistivity and these two admittance variations. On the other hand, BP and E_v are also simultaneously measured from the admittance signals following the gradual change of the chamber pressure based on the volume-oscillometric method. Experiments were successfully made in 14 subjects, showing that the indirect Hct values agreed well with the direct values obtained from sampled blood and that this simle technique was significant for the non-invasive ad simultaneous measurement of these physiological variables.