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It has been widely known that a telemetry system is useful for these studies, because the telemetry system can obtain physiological measurements from conscious and unrestrained laboratory animals. Maurey was the first to report on a telemetry experiment in the scientific literature (see Mackay, 1970). Mackay wrote the experiment as follows: “A rubber bulb detects the shortening of the pectoral muscle of a pigeon by its thickening the pneumatic signal traveling a rubber tube to a bulb pushing a stylus on a smoked arum. A flapping vane at the wingtip opens and closes an electric contact to indicate the relative duration of the period of elevation and depression of the wing.” One of the first telemetry experiments with the use of a radio signal is reported by Barr (1954). From the late 1950’s, several research groups have developed radio-telemetry devices for laboratory animals (Gold & Malcolm, 1957; Essler & Folk, 1961; Franklin, et al., 1964). Although telemetry technology for monitoring laboratory animals have already existed since the early 1950’s as described above, fully implantable and reliable telemetry devices for monitoring physiological functions in laboratory animals have been made commercially available since the late 1980’s. Advances and further miniaturization of the implantable devices in the beginning of 1990’s have provided to measure electrocardiogram (ECG), electromyogram (EMG), electroencephalogram (EEG), blood pressure (BP), body temperature (BT), and locomotor activity (LA). Therefore, the number of publications in which radio-telemetric results in laboratory animals has been tremendously increased for 2 decade. In these days, many companies commercially supply the radio-telemetry implants for monitoring physiological parameters. In this report, I would like to introduce a newly developed telemetry system in Japanese company and some useful software to analyze ECG data in the fields of cardiology and pathophysiology as well as pharmacology and toxicology. Further, I describe some experimental studies using a telemetry system and applications. 2. Newly developed telemetry system The telemetry system for rat and mouse consists of an implantable transmitter (ATE-01S) with a pair of flexible leads, a telemetry receiver (ATR-1001) and connected acquisition system (Softron ECG Processor; EP95) to personal computer (Fig. 1). ModernTelemetry 146 Fig. 1. Picture and schematic drawing of a newly developed telemetry system for recording ECGs. A telemetry transmitter is on a telemetry receiver. The implantable transmitter consists of a hermetically sealed plastic housing with a biocompatible silastic coating, occupying a volume of less than 1.9 ml and weighing approximately 3.8 g. Each transmitter contains an amplifier, a battery, radio-frequency electronics, a pair of flexible leads with 20 cm and a magnetically activated switch which allows the device to be turned on and off either in vivo or ex vivo. The transmitter passes the ECG signal to a receiver located beneath the animal cage via radio signal. The data acquisition system records and stores the raw telemetered data into the hard disk for subsequent analysis as described below (Section 4). 3. Transmitter implantation In many studies, the typical implantation procedure for monitoring ECG is positioning the body of the transmitter in the peritoneal cavity of the laboratory animals. However, we usually implant a telemetry transmitter for ECG chronically into the notal subcutanea under pentobarbital sodium anesthesia (40 mg/kg, intraperitoneally), because this procedure can easily perform and much less invasive and/or damaged for laboratory animals than in the peritoneal cavity procedure. Before making the incision in the skin of the animal, we use a clipper to remove the hair from the operation area of the anesthetized animal. The animal is placed on a hot plate to avoid hypothermia during procedure, and the operation area is sterilized with iodine. A 1.0-1.5 cm long incision in the skin is made, and transmitter is implanted into the subcutaneous area as shown in Fig. 2. Both electrodes are situated in the direction of the head of the animal. Paired electrodes of the transmitter are placed under the skin of the dorsal and ventral thorax to record the apex-base (A-B) lead ECG. When both electrodes are fixed on their places, the transmitter is activated by a magnet close to the transmitter body. When the battery of the transmitter is switched on, the heart beats are clearly audible within a few seconds. To complete the operation, the incision of skin is closed with absorbable suture or Michel clips. 4. Software for recording and analyzing of ECG from many points of view Softron ECG processor can connect to a telemetry receiver as well as a bioelectrical amplifier, a data recorder and a Holter ECG recorder for recording and analysis of ECGs. Many useful softwares are provided to record and analyze ECGs. In this section, I introduce these softwares. Recent Advances in Telemetry Monitoring and Analysis for Laboratory Animals 147 Fig. 2. Picture of a transmitter implantation in rat. 4.1 SP2000 SP2000 consists of the acquisition program and basic analyzing program for ECGs. The acquisition program can collect the data for a specific length of time or continuously and save it on the computer’s hard drive. The acquisition program consists of a Config, WaveIn, Replay, Edit, Print etc as shown in Fig. 3. Fig. 3. Main menu (left) and WaveIn screen (right) of SP2000. The Config (Configulation module) allows users to create a file that contains settings for detecting and collecting data signals during a study and to modify an existing configuration file for use in a different study. To record ECG waves, WaveIn is opened after setting of configulaton. The analyzing program calculates the points and characteristic values of an ModernTelemetry 148 ECG: characteristic points of the P, Q, R, S, T waves as well as the time intervals between these different points by Edit screen as shown in Fig. 4. The program can operate in automatic detection of complexes directly from the ECG signal. This detection is based on the presence of a R wave peak. Fig. 4. Edit screen of a mouse ECGs. 4.2 SBP2000 Although SP2000 is specific software for ECG, SBP2000 can record and analyze not only ECG but also intra ventricular pressure, blood pressure, blood flow and respiration. Operation is almost the same as SP2000. 4.3 SHL-2W SHL-2W is prepared for advanced analysis of arrhythmias for ECG. This software analyzes arrhythmias such as premature ventricular contraction (PVC), premature atrial contraction (PAC), ventricular tachycardia (VT), ventricular fibrillation (VF), Pause, etc based on patterns of QRS complex from long term recording ECGs obtained by the telemetry and Holter ECG recorder. Fig. 5 shows an example of mouse ECG recorded using the telemetry system. Some arrhythmias such as PVC are observed in this ECG. High lightened part is also shown below as an expanded window. Fig. 6 is Print Preview window. ECGs are able to print out as compress waves. Recent Advances in Telemetry Monitoring and Analysis for Laboratory Animals 149 Fig. 5. Long term ECGs of mouse represent with SHL-2W window. Fig. 6. Print preview window of compress ECGs. ModernTelemetry 150 4.4 SRV-2W SRV-2W is prepared for analysis of heart rate variability (HRV). I describe detail of the HRV in the next session. Breafly, this software detects R waves and calculated the R-R interval tachogram as the raw HRV in sequence order as shown in Fig. 7. Lorentz plots are also able to display. Fig. 7. Tachogram of the R-R interval (left) and example of Lorentz plots. From this tachogram, the average and instantaneous power spectra are obtained by the fast Fourier transform as shown in raight and left of Fig. 8, respectively. The software calculates many index of values of HRV as shown in Fig. 8. Fig. 8. Examples of average power spectrum (left) and 75 instantaneous power spectra (right) in mouse. 4.5 Other applications For further analysis of ECGs such as RR-QT relationship, software for Bootstrap method can apply after analyzing all of the waves. This software is useful to detect QT prolongation induced by drugs. Moreover, software for signal average electrocardiogram is developed to detect ventricular late potential. [...]... LF/HF References Mouse 5 76 1.9 0.5 4.9 Ishii et al (19 96) Vole 458 32 45 0.8 Ishii et al (19 96) Rat 337 14.1 2.1 6. 5 Kuwahara et al (1994) Guinea pig 244 6. 0 1.7 4.0 Akita et al (2002) Miniature pig 92 1987 2924 1.0 Kuwahara et al (1999) Thoroughbred horse 33 15 36 173 6. 8 Kuwahara et al (19 96) Table 2 The values of HRV obtained from each animal species 6. 2 Pathophysiological studies In the previous section,... 10 months control 10 months cacao ModernTelemetry HR (bpm) 1 96. 9 197.7 2 26. 4 185.2 SBP (mmHg) 93.9 85.7 96. 1 75.9 LF(msec2) HF(msec2) 80 .6 12.0 88.2 9.8 41.5 4.0 51.0 5.0 LF/HF 7 .6 14.0 10.9 9.9 Table 3 Effects of cacao liquor on cardiovascular and autonomic nervous functions Taurine is one of the most abundant free amino acids in animal tissues (Jacobsen, & Smith, 1 968 ) and possesses many important... and Identification of Some Minor Metabolites Phytochamistry 30: 165 7- 166 3 Rosas-Ballina, M., & Tracey, K.J (2009) Cholinergic Control of Inflammation J Internal Med 265 :66 3 -67 9 Rosengren, A., Tibblin, G., & Wilhelmsen, L (1991) Self-perceived Psychological Stress and Incidence of Coronary Artery Disease in Middle-aged Men Am J Cardiol 68 ; 1171-1175 Ruberman, W., Weinblatt, E., & Goldberg, J.D (1984)... biotelemetry data are radio waves Due to the proliferation of biotelemetry in recent years, the Federal 166 ModernTelemetry Communications Commission (FCC) has allocated dedicated frequency bands for biotelemetry use in the VHF range, generally over 100 MHz Typically variables that have been monitored through biotelemetry fall in four categories: (1) Bioelectrical such as ECG, EMG, and EEG; (2) physiological... Analysis of Heart Rate Variability in the Horse J Auton Nerv Syst 60 : 43-48 Kuwahara, M., Hashimoto, S., Tsubone, H., & Sugano, S (19 96) Developmental Changes of Autonomic Nervous Activity in Spontaneously Hypertensive Rats: Investigation by Power Spectral Analysis of Heart Rate Variability J Ambulatory Monitoring 9(1): 51-58 164 ModernTelemetry Kuwahara, M., Kawaguchi, T., Ito, K., & Tsubone, H (2009)... Pacing and Electrophysiology, 19 96) 152 ModernTelemetry Fig 9 Power spectrum obtained from human 6 Applications of power spectral analysis of HRV in laboratory animals HRV has provided increasing interest as a noninvasive index of autonomic nervous activity (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 19 96) Because we thought that the... 241: H620-H629 Inagaki, H., Kuwahara, M., & Tsubone, H (2004) Effects of Psychological Stress on Autonomic Control of Heart in Rats Exp Anim 53(4): 373-378 Ishii, K., Kuwahara, M., Tsubone, H., & Sugano, S (19 96) Autonomic Nervous Function in Mice and Voles (Microtus arvalis): Investigation by Power Spectral Analysis of Heart Rate Variability Lab Anim 30(4): 359- 364 Jacobsen, J.G., & Smith, L.H (1 968 )... the sensor sampling frequency, and the data transmission rate To prolong the life of the battery in an implanted 168 ModernTelemetry biotelemetry system, some researchers have experimented with remote power switching (Varosi et al., 1989, as cited in Hamrita et al., 1998; Leung et al, 19 86, as cited in N F Güler & Übeyli, 2002) In order to select the best transmitter for a given application, all the... fields have had to design and develop their own biotelemetry systems in an attempt to improve on existing commercially developed ones (I Güler & Kara, 19 96; Wouters et al, 1994, and Kettlewell et al, 1997, as cited in Strydis, 2005; Ackermann et al., 20 06; Silva et al., 2005) or to meet specific monitoring needs (Lowe et al., 2007; Quwaider 170 ModernTelemetry et al, 2010; Cross et al., 2004) In some... ratio These results suggest that autonomic balance becomes predominant in sympathetic 160 ModernTelemetry nervous activity in both anxiety-like and fear-like states These changes in rats correspond to changes which are relevant to cardiovascular diseases under many kinds of psychological stress (Inagaki, et al., 2004) 6. 2.4 Hypoxia and inflammation Hypoxia induces a range of behavioural, cardiopulmonary, . Modern Telemetry 158 Group HR (bpm) SBP (mmH g ) LF(msec 2 ) HF(msec 2 ) LF/HF 5 months control 1 96. 9 93.9 80 .6 12.0 7 .6 5 months cacao 197.7 85.7 88.2 9.8 14.0 10 months control 2 26. 4. Homeostasis; 36 :67 - 82. Widgren BR, Wikstrand J, Berglund G & Andersson OK 1992. Increased response to physical and mental stress in men with hypertensive parents. Hypertension;20 :60 6- 61 1. Wilkins. (19 96) Rat 337 14.1 2.1 6. 5 Kuwahara et al. (1994) Guinea pig 244 6. 0 1.7 4.0 Akita et al. (2002) Miniature pig 92 1987 2924 1.0 Kuwahara et al. (1999) Thoroughbred horse 33 15 36 173 6. 8