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Radiotelemetry measurement of heart rate, blood pressure and locomotory activity of rats in physiological experiment

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Evaluation of physiological traits in freely moving animals represents an innovative approach allowing physiological studies in undisturbed animals without interference with handling and stress. This approach is important in behavioural sciences and research on physiological basis of cardiovascular diseases. Recently, there is only one such system in the world that enables simultaneous measurement of blood pressure, heart rate, body temperature and electroencephalography together with the locomotory activity which was developed by the Data sciences International (st. Paul, Minessota, Usa). In our laboratory we have introduced and validated this system in laboratory rats and hereby present results on blood pressure, heart rate and locomotory activity in rats exposed to stabile light – dark cycles.
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INTRODUCTION
Measurements of physiological variables in
experiments are frequently affected by irregularities
resulting from handling of animals and subsequent
stress. These limitations can be overcome by telemetric
techniques which enable obtaining data without
handling of experimental animals before and during
measurements.
Determination of blood pressure (BP) and heart
rate (HR) is very useful in many types of experiments.
Usually BP is measured by tail-cuff plethysmography on
the tail of laboratory rodents, mainly rats and mice. This
“noninvasive” approach requires handling of animals
and an increase of ambient temperature that result in the
RADIOTELEMETRY MEASUREMENT OF HEART RATE,
BLOOD PRESSURE AND LOCOMOTORY ACTIVITY OF RATS IN
PHYSIOLOGICAL EXPERIMENT
1*11,2
1
2
ABSTRACT
 
undisturbed animals without interference with handling and stress. This approach is important in behavioural sciences and research
on physiological basis of cardiovascular diseases. Recently, there is only one such system in the world that enables simultaneous
measurement of blood pressure, heart rate, body temperature and electroencephalography together with the locomotory activity
 
validated this system in laboratory rats and hereby present results on blood pressure, heart rate and locomotory activity in rats

Key words: 


approach for measuring BP and HR is a radiotelemetric
method. The direct comparison of both methods revealed
that the radiotelemetry provided results about 16 ± 2

al., 1990).
In our experiment we aimed at validation of the
radiotelemetry method for measurement of BP, HR and
locomotory activity. This type of measurement may
provide valuable data especially in continuous long-term-term
experiments. Therefore, we evaluated especially long
term changes of these physiological variables during
circadian rhythms which cannot be assessed by the
noninvasive tail-cuff plethysmography.
*Correspondence:
 

 63
Slovak J. Anim. Sci., 42, 2009, SUPPLEMENT 1: 63-66
© 2009 CVŽV Nitra
ISSN 1337-9984

Original paper Slovak J. Anim. Sci., 42, 2009, SUPPLEMENT 1 : 63-66
MATERIAL AND METHODS
In our experiment we used four mature female
  
    

 
     

administered intramuscularly 600 µl of mixture to 300g

                     
       
   
afterwards radiotelemetry measurements were initiated.
 
activity on freely moving animals we used the
     
       
only one available for this type of measurement. The
system consists from telemetric implants which send
signals to receivers located under the cages in which
animals were individually housed. The receiver converts
measured data and sends them to the matrix connected

that enables recording and storage of results. In our

   
into the abdominal aorta closely to the point of its

        
after the surgery. Data for analysis of circadian rhythms
   
experimental animals exhibited normal behaviour and no
consequences of surgery.
Data were analyzed by the software Dataquest
       
     

RESULTS AND DISCUSSION
       
       
       
intervals. This mode of measurement provided us with
approximately 60,000 records from each animal per
parameter and one day. Representative records of daily

          


values during the light-time were found in a range 60
90 mmHg for diastolic BP, with the mean 71.7 ± 0.1

   


and systolic BP, respectively. HR values during the ligh-

         

          


was accompanied by an increase in BP and HR. Mean
locomotory activity during the light-time was 0.8 ± 0.1

up to 3.2 ± 0.1 counts per minute. Measured values
of BP and HR are in ranges reported with telemetric
measurements and are lower as found by noninvasive tail-

become possible to use the telemetric system in different



In all variables we found an increase of values

circadian control of all studied parameters including the
anticipatory increase before the change in the photoperiod.

and locomotory activity we observed rhythmic changes
 
rhythms with period 2-3 hours were much more variable
than the circadian rhythms and their characteristics,
which have not been described well yet.



rhythmic changes with longer periods and demonstrated
     
        
correlated closely between diastolic and systolic BP as

2). Multiple correlations among all studied parameters
       
bioinformatics approach owing to the huge number of
obtained data.
CONCLUSION
     
radiotelemetry techniques for continuous and long term
monitoring of BP, HR and locomotory activity in freely
moving rats. The ranges of obtained values of systolic
and diastolic BP were in the range given in literature.
      
of physiological variables without an interference

Slovak J. Anim. Sci., 42, 2009, SUPPLEMENT 1: 63-66 Original paper
with handling and subsequent stress stimuli of studied

and exchange of batteries in sensors by the manufacturer.
Therefore the use of the system must be carefully
considered.
Fig.1: Daily proles of heart rate (A), locomotor activity (B) and blood pressure (C) in a laboratory rat
implanted with the sensor TA11PA-C40 (DSI St. Paul, Minnesota, USA). Plots represent outputs
from the program Dataquest A.R.T. 4.1 with 8.640 values per 24 h reecting 1 min averages of
measured parameters. Animals were kept at LD 12:12, with lights on from 22:00 till 10:00. The dark
bar above graphs represents the dark time period
Acknowledgements


66
Original paper Slovak J. Anim. Sci., 42, 2009, SUPPLEMENT 1 : 63-66
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      

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behaviours associated with de-arousal in restricted-fed
Physiology and Behavior

         
Measurement of intraocular pressure by telemetry in
conscious, unrestrained rabbits. Investive Ophthalmology
and Visual Science





Laboratory Animals
  

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Fig.2: Daily proles of heart rate (A), locomotor activity (C) and blood pressure (systolic (B) and diastolic
(D)) in the laboratory rat kept in LD 12:12 and monitored by the radiotelemetry system (DSI St.
Paul, Minnesota, USA). Each point at the graph represents a 1-hour mean. Results illustrate a high
correlation between systolic and diastolic BP values and between heart rate and locomotor activity.
The dark bar on the abscissa represents the dark period of the 24 h cycle
... In the presented study, significant increase in LVEDP together with protected LV systolic function (characterized with mild reduction in EF) is in line with heart failure with preserved EF [3]. Although we observed a significant decrease in MBP after MI, this decrease is within physiological limits and does not reflect a significant hypotension [21]. ...
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Background and objective: Heart failure (HF) is a common complication of cardiovascular disease, which leads to functional cardiac abnormalities. Beta-blockers are commonly used to reduce mortality in HF patients; however, they are associated with an increased risk of erectile dysfunction (ED). Nebivolol is a third-generation beta-blocker with also having a Nitric oxide (NO) releasing effect. NO plays a key role in penile erection. The aim of this study was to investigate the NO-mediated effects of nebivolol on ED in HF. Material and methods: Twenty-four weeks old rats were divided into three groups: sham-operated control (SC), HF-induced control (HFC), and nebivolol-treated (HFNEB). HF was induced by the ligation of the left anterior descending coronary artery. Eight weeks after the ligation, functional, hemodynamic, biologic, and histologic studies were conducted to assess NO-mediated effects of nebivolol. Results: HF rats displayed impaired erectile function represented by decreased intracavernosal/mean arterial pressure ratio (ICP/MAP). Increased nitrosative damage/decreased antioxidant capacity was consistent with decreased endothelial NOS (eNOS) and increased inducible NOS (iNOS) and neuronal NOS (nNOS) immunoreactivity in this group. Nebivolol treated animals were characterized by improved functional capacity, increased antioxidant and decreased oxidant capacity. Prevention of eNOS and an increase in nNOS immunoreactivity was also significant in this group. Conclusion: Our study showed the positive effects of nebivolol on erectile function in HF. NO-mediated mechanisms behind this effect can be summarized as eNOS mediated dilation of the cavernous body and nNOS mediated smooth muscle relaxation. To the best of our knowledge, this study is the first in the literature to discuss all three NOS isoforms in order to explain the NO-mediated effects of nebivolol in ED.
... The significant increase in LVEDP, despite the protection of LV systolic function, is in line with the HFpEF model (16). Although we observed a significant decrease in MBP after MI, this decrease is within physiological limits and does not reflect a significant hypotension (17). Our results are in line with Cho et al. (18) and suggest that renal hypoperfusion is not a primary factor in the development of CRS. ...
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Objectives: Despite several proposed mechanisms for the pathophysiology of cardiorenal syndrome (CRS), the exact mechanism remains unclear. Nitrosative stress has been argued as a key mechanism recently. Nebivolol is a beta-blocker with nitric oxide (NO)-releasing effect. In the present study, NO-mediated effects of two different treatment regimes of nebivolol in CRS were studied. Materials and methods: Rats were divided into: sham-operated (sham-control), myocardial infarction (MI)-induced, (MI-control) early nebivolol-treated (MI-neb1) and late nebivolol-treated (Mı-neb2) groups. The effects of nebivolol were assessed both in the early and late period of MI by histologic, hemodynamic and biologic studies. Results: Developed MI model was in line with the heart failure with preserved ejection fraction. Focal and total tubular damage findings were observed in MI-control group both in early and late period of MI. In parallel, subclinical functional damage was transformed into chronic renal dysfunction in this group. Increased inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) together with decreased neuronal NOS (nNOS) levels were in parallel with the increased inflammation and nitrosative stress biomarkers. Nebivolol effectively prevented both subclinical and clinical nephropathy. There was no statistical difference between the nebivolol treatment regimes. Conclusion: The beneficial effects of nebivolol were closely related to the reduction of nitrosative damages as well as hemodynamic alterations. The NO-mediated effects were: prevention of nitrosative damage by decreasing iNOS, preservation of nNOS in order to maintain glomerular filtration rate (GFR), and restoration of eNOS in the late period of MI. On contrary to our previous work, early nebivolol administration had a similar effect with delayed administration of nebivolol on CRS.
... The first technique consists of direct observation using interval and ordinal scales. The second approach to quantify locomotor activity includes video-based systems (Pierce and Kalivas, 1997), infrared light beams recorder (Galani et al., 2001), radiotelemetry system (Molčan et al., 2009), open field test (Daniels et al., 2009) and RW s (Jud et al., 2005). ...
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Locomotor behaviour is regarded as a fundamental index of general animal activity. Circadian rhythms (CRs) of locomotor activity are one of the most prominent biological rhythms which synchronize to the natural environmental light -dark cycle (LD). The present study aims to develop a reliable and precise setup for long-term recordings of the CRs in laboratory rodents (e.g. rats, hamsters, and mice). The recording setup consists of accessible running wheels (RW) in animal cages. Revolutions of RW were acquired through a circuit supported by either magnetic reed or inf rared (photocell) switch sensors. Data acquisition and analysis were control led through proper software. In a series of experiments, the CRs patterns were successfully recorded under LD, as well as constant darkness (DD) conditions. In summary, the recording setup enabled, with an acceptable precision, to record and analyses the animal 's circadian locomotor activity patterns automatically without upsetting its behaviour pattern. Measurements and analysis of CRs of locomotor activities using this setup could be applied in various research issues such as chronobiological, neuroethological, physiological, and pharmacological studies.Egypt. J. Exp. Biol. (Zool.
... The catheter was then stabilized to the aorta with tissue glue (3M Vetbond; DSI, USA) and a cellulose patch (Cellulose Patch Kit -Small Animals; DSI, USA). The body of the 1ransmitter was secured to the muscular wall and the whole procedure has been validated at our department previously (Molcan et al. 2009). Animals were inclllded in the experiment two weeks after the surgical procedure. ...
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Disturbed circadian activity of the sympathetic system may be involved in negative consequences of chronodisruption on the cardiovascular system. We studied daily changes in pressure response to adrenergic stimulation in rats exposed to repeated phase advance shifts (PAS) of light/dark (LD) regimen. Blood pressure (BP), heart rate (HR) and locomotor activity was measured by radiotelemetry in normotensive Wistar rats exposed to repeated PAS (three 8-h shifts per week) lasting for 12 weeks. Norepinephrine was administered subcutaneously in the middle of L and D during week 12 of PAS exposure. In the control LD cycle, cardiovascular parameters exhibited significant daily rhythms with expected higher values during D than L phase. Rats exposed to PAS showed disturbed rhythms without a BP and HR increase. Administration of norepinephrine to control rats revealed daily variability in the cardiovascular response with higher stimulation of BP during L than D. This daily pattern of BP response to norepinephrine was diminished in the PAS group. The damped daily variability in pressure response to norepinephrine and augmented response during the light phase of the day suggest that the increased and desynchronised activity of the sympathetic system may worsen responses of the cardiovascular system to load in individuals exposed to irregular LD conditions.
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Although exercise is usually associated with beneficial effects on physical and mental health, patients recovering from surgery may be hampered to perform active exercise. Whole body vibration (WBV) is suggested a passive alternative for physical training. Aim of the present study was to explore the therapeutic potential of WBV compared to physical exercise during early post-surgery recovery. Male three months old Wistar rats underwent major abdominal surgery. Starting the day after surgery, rats were subjected to either daily WBV or exercise (treadmill running) for 15 consecutive days. Control rats underwent pseudo treatment. During the first week after surgery, effects of interventions were obtained from continuous recording of hemodynamic parameters, body temperature and activity (via an implanted transducer). Behavioral tests were performed during the second post-surgical week to evaluate anxiety-like behavior, short and long-term memory functions, cognitive flexibility and motor performance. Animals were sacrificed 15 days after surgery and brain tissue was collected for analysis of hippocampal neuroinflammation and neurogenesis. Surgery significantly impacted all parameters measured during the first post-surgery week, irrespective of the type of surgery. Effect on cognitive performance was limited to cognitive flexibility; both WBV and exercise prevented the surgery-induced decline. Exercise, but not WBV increased anxiety-like behavior and grip strength. WBV as well as exercise prevented the surgery-induced declined neurogenesis, but surgery-associated hippocampal neuroinflammation was not affected. Our results indicated that active exercise and WBV share similar therapeutic potentials in the prevention of surgery induced decline in cognitive flexibility and hippocampal neurogenesis. In contrast to exercise, WBV did not increase anxiety-like behavior. Since neither intervention affected hippocampal neuroinflammation, other mechanisms and/or brain areas may be involved in the behavioral effects. Taken together, we conclude that WBV may provide a relevant alternative to active exercise during the early stage of post-operative recovery.
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Embryos of rats with inherited stress-induced arterial hypertension (ISIAH strain) were transferred to normotensive Wistar rats. Cryopreservation of these embryos was used in some trials. Rats developed to term after freezing-thawing of ISIAH embryos and their transfer to Wistar recipients demonstrated a significant decrease in arterial blood pressure (ABP) both in males and females under basal conditions and stress. The effect persisted in subsequent generation obtained from crosses between these animals. In the control series (cryopreservation omitted), transferring of ISIAH embryos to Wistar recipients did cause a decrease; but even ABP increased in offspring. In this experimental series of transferring the unfrozen embryos, ABP of recipient Wistar rats was significantly increased. We have also found behavioral differences between cryopreserved and control rats. Startle reflex was decreased in offspring developed after cryopreservation and embryo transferring of ISIAH rats to Wistar recipients, as compared to initial ISIAH and Wistar rats. Taken together, these experimental data strongly support the hypothesis that embryo freezing and embryo transferring can have delayed consequences for offspring as well as for recipients.
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The effects of assisted reproductive technologies on the development of hypertensive phenotype were reviewed. Special attention was paid to the effects of cultivation and transplantation of preimplantation embryos on arterial pressure in individuals developed from these embryos. The analysis of studies performed on the laboratory models (mostly on hypertensive strains of rats) was performed. These data were discussed in the context of application of assisted reproductive technologies in medicine.
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Radiotelemetry is the "state of the art" for monitoring physiological functions in awake and freely moving laboratory animals, while minimizing stress artifacts. For researchers, especially those in the fields of pharmacology and toxicology, the technique provides a valuable tool for defining the physiological and pathophysiological consequences derived from advances molecular, cellular, and tissue biology and in predicting the effectiveness and safety of new compounds in humans. There is ample evidence that radiotelemetry systems for measuring physiological functions has been sufficiently validated. Today, the technology is an important tool for collection of a growing number of physiological parameters, for contributing to animal welfare (reduction and refinement alternatives), and for reducing overall animal research costs.
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Radiotelemetry provides an alternative means of obtaining physiological measurements from conscious and freely moving animals, without introducing stress artefacts. A surgical procedure is described for implanting radiotelemetry transmitters to monitor the electrocardiogram (ECG), heart rate (HR) and body temperature (BT) in small goldfish (Carassius auratus; 50-100 g) and Prussian carp (Carassius auratus gibelio; 100 g). This type of transmitter is commonly implanted in freely moving mice. After surgery and a recovery period of 24 h, the ECG, HR and BT were recorded in freely swimming fish within the limitations of the aquarium.
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A chronic, indwelling, tail arterial cannula was implated in conscious undisturbed rats for measurement of blood pressure and heart rate and for obtaining blood samples. As an index of sympathetic activity, plasma levels of catecholamines in arterial blood of conscious animals were assayed by a radioenzymatic, paper-chromatographic procedure. Blood pressures of unrestrained spontaneously hypertensive (SHR) rats in their home cages (161 +/- 3/141 +/- 4 mmHg) were not different from those of pentobarbitol-anesthetized, hypertensive animals but were about 25 mmHg lower than awake animals during the restraint required for the tail-cuff procedure. Basal levels of plasma catecholamines in awake, undisturbed or in pentobarbital-anesthetized animals were similar in age-matched SHR and normotensive Wistar-Kyoto (WKY) rats. SHR rats were shown to have greater increase in plasma catecholamines than WKY rats during forced immobilization or restraint for indirect measurement of blood pressure.
Chronic measurements of systemic arterial blood pressure and heart rate via a chronically implanted telemetric transmitter in unrestrained rats, was validated in a three-phase study. In the first part, week-to-week variability of systolic, diastolic, and mean arterial pressures, and heart rate was found to be minimal over the course of nine weeks. In the second part, the reproducibility of cardiovascular response to three successive administration of sotalol, an antihypertensive agent, was studied. In the last part, cardiovascular parameters determined by telemetry were compared to those obtained by direct arterial catheterization and showed a good linear correlation between those two methods.
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The heating and restraint inherent to tail-cuff measurement of systolic blood pressure (SBP) in rats may alter SBP and introduce a 'biological' error in its estimation by this technique. This problem was examined in unanesthetized normotensive and hypertensive rats fitted with an arterial catheter. All SBP values recorded in unrestrained rats during a 2 h period were averaged by computer and compared with intra-arterial SBP measurements observed while the rat was being subjected to the tail-cuff procedure. With the latter procedure, SBP was 16 +/- 2 mmHg lower in normotensive rats (P less than 0.001) and 7 +/- 3 mmHg higher in hypertensive rats (P less than 0.05) than when the rats were unrestrained. The effects of heat and restraint, both separately and in combination, on SBP were evaluated during four additional 30-min monitoring periods. In both groups of rats, restraint failed to alter SBP and heat lowered it slightly. The two stimuli, combined, lowered SBP in normotensive rats, but raised it by 12 +/- 2 mmHg in hypertensive rats (P less than 0.01). Thus, tail-cuff SBP measurements represent under- and overestimates in normotensive and hypertensive rats, respectively, since the two groups respond to the procedure in opposite manners.
We examined the influence of procedures used in blood pressure measurement on blood pressure and the effects of antihypertensive agents. Subjects were spontaneously hypertensive rats (SHR) and their Wistar/Kyoto (WKY) controls. Blood pressure was recorded by telemetry. Twenty-four h baseline pressure were measured, and the effect of minor handling on blood pressure and heart rate was examined. The influence of restraint such as is used for tail-cuff blood pressures was examined. The effects of three different antihypertensive drugs was also examined in the SHR. In the home-cage environment, the SHRs showed higher systolic blood pressures, but had similar hypertensive responses to minor handling as the WKYs. Both strains had elevated heart rate and blood pressure when restrained in the manner used for tail-cuff readings. The antihypertensive effects of captopril and losartan in the SHR were unchanged when the animals were restrained but the hypotensive effect of hydralazine was greater. These results confirm that significant changes in heart rate and blood pressure can occur as a result of the minor procedures frequently used in blood pressure recording in both SHR and WKY rats. This suggests that telemetry may have significant advantages as a method for continuous blood pressure monitoring. The pharmacological profile of antihypertensive drugs may well be different in animals where telemetry is employed and are not subject to the stresses involved in previous methods of monitoring blood pressure.
  • P Zuther
ZUTHeR, P. -leMMeR B. 2004. Chronos-Fit, http://www. ma.uni-heidelberg.de/inst/phar/forschunglemmer.html, 2004.