Implantable Telemetry System Research Articles

Collaborative Cross mice have diverse phenotypic responses to infection with Methicillin-resistant Staphylococcus aureus USA300.

Staphylococcus aureus (S. aureus) is an opportunistic pathogen causing diseases ranging from mild skin infections to life threatening conditions, including endocarditis, pneumonia, and sepsis. To identify host genes modulating this host-pathogen interaction, we infected 25 Collaborative Cross (CC) mouse strains with methicillin-resistant S. aureus (MRSA) and monitored disease progression for seven days using a surgically implanted telemetry system. CC strains varied widely in their response to intravenous MRSA infection. We identified eight 'susceptible' CC strains with high bacterial load, tissue damage, and reduced survival. Among the surviving strains, six with minimal colonization were classified as 'resistant', while the remaining six tolerated higher organ colonization ('tolerant'). The kidney was the most heavily colonized organ, but liver, spleen and lung colonization were better correlated with reduced survival. Resistant strains had higher pre-infection circulating neutrophils and lower post-infection tissue damage compared to susceptible and tolerant strains. We identified four CC strains with sexual dimorphism: all females survived the study period while all males met our euthanasia criteria earlier. In these CC strains, males had more baseline circulating monocytes and red blood cells. We identified several CC strains that may be useful as new models for endocarditis, myocarditis, pneumonia, and resistance to MRSA infection. Quantitative Trait Locus (QTL) analysis identified two significant loci, on Chromosomes 18 and 3, involved in early susceptibility and late survival after infection. We prioritized Npc1 and Ifi44l genes as the strongest candidates influencing survival using variant analysis and mRNA expression data from kidneys within these intervals.

Surgical removal of a telemetry system in a cynomolgus monkey (Macaca fascicularis): a 12-month observation study

BackgroundTelemetry is a wireless implanted device that measures biological signals in conscious animals and usually requires surgery for its removal when the study is finished. After removing the device, the animals are either used for other studies or euthanatized.Case presentationHerein, we report the case of a living cynomolgus monkey (Macaca fascicularis) that was used for the entire experimental period, instead of euthanasia, after surgical removal of an implanted telemetry system. Radiography was used to determine the status of the implanted telemetry, following which, a repair surgery was performed for removing the system; clinical signs were used to preserve the life of the cynomolgus monkey. Postoperative clinical signs, food consumption, hematology, and serum biochemistry were examined during the 12-month observational period. No abnormal readings or conditions were observed in the subject after implant removal.ConclusionsThis study may be a useful case report for living cynomolgus monkeys in telemetry implantations used throughout the study period. We suggest minimizing the suffering and improving the welfare of these animals.

Daily inhalation of hydrogen gas has a blood pressure-lowering effect in a rat model of hypertension

A recent clinical study demonstrated that haemodialysis with a dialysate containing hydrogen (H2) improves blood pressure control in end-stage kidney disease. Herein, we examined whether H2 has a salutary effect on hypertension in animal models. We subjected 5/6 nephrectomised rats to inhalation of either H2 (1.3% H2 + 21% O2 + 77.7% N2) or control (21% O2 + 79% N2) gas mixture for 1 h per day. H2 significantly suppressed increases in blood pressure after 5/6 nephrectomy. The anti-hypertensive effect of H2 was also confirmed in rats in a stable hypertensive state 3 weeks after nephrectomy. To examine the detailed effects of H2 on hypertension, we used an implanted telemetry system to continuously monitor blood pressure. H2 exerted an anti-hypertensive effect not only during daytime rest, but also during night-time activities. Spectral analysis of blood pressure variability revealed that H2 improved autonomic imbalance, namely by suppressing the overly active sympathetic nervous system and augmenting parasympathetic nervous system activity; these effects co-occurred with the blood pressure-lowering effect. In conclusion, 1-h daily exposure to H2 exerts an anti-hypertensive effect in an animal model of hypertension.

Cyclic Pattern of Intraocular Pressure (IOP) and Transient IOP Fluctuations in Nonhuman Primates Measured with Continuous Wireless Telemetry

ABSTRACTPurpose: Most studies on intraocular pressure (IOP) to monitor IOP “fluctuations” in glaucoma patients have been performed with snapshot tonometry techniques that obtain IOP measurements at single time points weeks to months apart. However, IOP telemetry has shown that IOP varies from second-to-second due to blinks, saccades, and systolic vascular filling. The purpose of this study was to characterize the cyclic pattern of baseline IOP and transient IOP fluctuations in 3 nonhuman primates (NHPs).Methods: Bilateral IOP was measured using a proven implantable telemetry system and recorded 500 times per second, 24 hours a day, up to 451 continuous days in 3 male rhesus macaques aged 4 to 5 years old. The IOP transducers were calibrated every two weeks via anterior chamber cannulation manometry and all data were continuously corrected for signal drift via software, filtered for signal noise and dropout, and peaks and troughs were quantified and counted using a finite impulse response filter; waking hours were defined as 6:00–18:00 hours based on room light cycle.Results: Fourier transform analyses of baseline IOP and the hourly mean frequency of transient IOP fluctuations > 0.6 mmHg, 0.6–5 mmHg and > 5 mmHg above baseline during waking hours exhibited an approximate 16- to 91-day cyclic pattern in all NHPs. There were no measured environmental or experimental factors associated with this cyclical pattern.Conclusions: While the importance of the cyclic pattern identified in IOP and its fluctuations is unknown at this time, it is plausible that this pattern is relevant to both homeostasis and pathophysiology of the ONH, corneoscleral shell, and aqueous outflow pathways.

IOP, IOP Transient Impulse, Ocular Perfusion Pressure, and Mean Arterial Pressure Relationships in Nonhuman Primates Instrumented With Telemetry.

PurposeTo characterize relationships between intraocular pressure (IOP), mean arterial pressure (MAP), ocular perfusion pressure (OPP), IOP transient impulse, and IOP baseline impulse using continuous telemetry in nonhuman primates.MethodsWe used our validated implantable telemetry system to wirelessly record bilateral IOP and arterial BP at 500 Hz in 7 eyes of 4 male rhesus macaques, aged 4 to 5 years. IOP, MAP, OPP, IOP transient impulse, and IOP baseline impulse were averaged into 1-hour periods over 20 days for each NHP. IOP transient impulse was defined as the portion of total IOP due to transient IOP fluctuations <0.5 seconds duration alone and IOP baseline impulse as the remaining area under the IOP versus time curve. OPP was defined as arterial BP-IOP (calculated continuously), and MAP was the hourly average of the continuous BP curve. Relationships between the variables were analyzed for each 24-hour period using either multivariate linear regression or Spearman Correlation Coefficients as appropriate.ResultsOver twenty 24-hour periods, IOP transient impulse and OPP showed significant positive relationship in all eyes, which was driven largely by the data during waking hours. There was no significant relationship between IOP and MAP, IOP transient impulse and MAP, or IOP baseline impulse and IOP transient impulse.ConclusionsThere are significant positive relationships between the frequency and/or size of transient IOP fluctuations (IOP transient impulse) and OPP. A possible explanation of this finding is that higher OPP, as well as a greater number of blinks and saccades (the primary sources of IOP transients), are associated with increased activity.

A Multi-Sensor and Parallel Processing SoC for Miniaturized Medical Instrumentation

We report VivoSoC , a system-on-chip realized in 130-nm CMOS for miniaturized medical instrumentation as used in mobile health devices or implantable telemetry systems for animal experiments. It features six neural stimulation channels and acquisition circuits for 9 $\times $ electrode-based recordings, 4-channel/32-LED photoplethysmography (PPG), bioimpedance, and temperature. A 34- $\mu \text{W}$ /MHz quad-core processing unit with sophisticated data, power, and clock management techniques enables on-chip feature extraction, which can dramatically reduce transmission or storage data rates in a system—crucial for overall power consumption and exemplarily demonstrated on preliminary work on implantable PPG-based vital signs monitoring.

HCN4-Overexpressing Mouse Embryonic Stem Cell-Derived Cardiomyocytes Generate a New Rapid Rhythm in Rats with Bradycardia.

A biological pacemaker is expected to solve the persisting problems of an artificial cardiac pacemaker including short battery life, lead breaks, infection, and electromagnetic interference. We previously reported HCN4 overexpression enhances pacemaking ability of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) in vitro. However, the effect of these cells on bradycardia in vivo has remained unclear. Therefore, we transplanted HCN4-overexpressing mESC-CMs into bradycardia model animals and investigated whether they could function as a biological pacemaker. The rabbit Hcn4 gene was transfected into mouse embryonic stem cells and induced HCN4-overexpressing mESC-CMs. Non-cardiomyocytes were removed under serum/glucose-free and lactate-supplemented conditions. Cardiac balls containing 5 × 103 mESC-CMs were made by using the hanging drop method. One hundred cardiac balls were injected into the left ventricular free wall of complete atrioventricular block (CAVB) model rats. Heart beats were evaluated using an implantable telemetry system 7 to 30 days after cell transplantation. The result showed that ectopic ventricular beats that were faster than the intrinsic escape rhythm were often observed in CAVB model rats transplanted with HCN4-overexpressing mESC-CMs. On the other hand, the rats transplanted with non-overexpressing mESC-CMs showed sporadic single premature ventricular contraction but not sustained ectopic ventricular rhythms. These results indicated that HCN4-overexpressing mESC-CMs produce rapid ectopic ventricular rhythms as a biological pacemaker.

Chronic Cardiac Output measurements in unrestrained rats: Surgical description

Measurement of systemic blood flow and cardiac output in awake but restrained rats has previously been possible via complicated tether and electrical commutator systems that are no longer widely available. A new, fully implantable telemetry system with modified transit-time volume flow probes, allows ascending aorta flow (cardiac output minus coronary flow) measurements in unrestrained rats over extended periods of time. A surgical protocol (adapted from Thomas L. Smith, PhD. Dept. of Orthopaedic Surgery, Wake Forest Baptist Health) was developed for the chronic implantation of the flow probe around the rat ascending aorta, with subcutaneous tunneling of the flowprobe cable to the implant site and securing of the telemetry unit in the abdominal cavity. Animals may be deeply anesthetized with 5% isoflurane and directly intubated transpharyngeally to avoid use of long lasting injectable anesthetics. The pectoral muscles are bisected to expose the transversus costarium crossing the 3rd intercostal space (surgical approach to the aorta) to insert on the 4th rib. The thoracic cavity is opened ~ 3 mm lateral to the sternum to avoid the internal mammary artery and extended dorsally ~ 1 cm. The 3rd intercostal space is expanded with a lacrimal sac retractor to permit reflection of the lung and thymus allowing exposure of the superior vena cava and ascending aorta. A 5 mm section of the aorta is isolated from the vena cava and pulmonary artery and sutures are placed around the aorta. The flow probe is placed in midsternal position and sutures are used to position the aorta into the probe lumen. The intercostal space is closed with 3 sutures and the probe cable secured with the telemetry implant located in the abdomen. The chest is evacuated and surgical incisions are closed. This technique permits long term internal battery or inductively powered assessment of cardiac output along with ECG and/or arterial pressure measurements. This is particularly important for vascular resistance determinations and also other applications that require simultaneous measurements of flow, pressure and ECG in small animals. Telemetry data from rat at day 6 post implantation. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The evaluation of endpoint variability and implications for study statistical power and sample size in conscious instrumented dogs

IntroductionThe sensitivity of a given test to detect a treatment-induced effect in a variable of interest is intrinsically related to the variability of that variable observed without treatment and the number of observations made in the study (i.e. number of animals). To evaluate test sensitivity to detect drug-induced changes in myocardial contractility using the variable LVdP/dtmax, a HESI-supported consortium designed and conducted studies in chronically instrumented, conscious dogs using telemetry. This paper evaluated the inherent variability of the primary endpoint, LVdP/dtmax, over time in individual animals as well as the variability between animals for a given laboratory. An approach is described to evaluate test system variability and thereby test sensitivity which may be used to support the selection of the number of animals for a given study, based on the desired test sensitivity. MethodsA double 4 × 4 Latin square study design where eight animals each received a vehicle control and three dose levels of a test compound was conducted at six independent laboratories. LVdP/dtmax was assessed via implanted telemetry systems in Beagle dogs (N = 8) using the same protocol and each of the six laboratories conducted between two and four studies. Vehicle data from each study was used to evaluate the between-animal and within-animal variability in different time averaging windows. Simulations were conducted to evaluate statistical power and type I error for LVdP/dtmax based on the estimated variability and assumed treatment effects in hourly-interval, bi-hourly interval, or drug-specific super interval. ResultsWe observe that the within-animal variability can be reduced by as much as 30% through the use of a larger time averaging window. Laboratory is a significant source of animal-to-animal variability as between-animal variability is laboratory-dependent and is less impacted by the use of different time averaging windows. The statistical power analysis shows that with N = 8, the double Latin square design has over 90% power to detect a minimal time profile with a maximum change of up to 15% or approximately 450 mm Hg/s in LVdP/dtmax. With N = 4, the single Latin square design has over 80% power to detect a minimal time profile with a maximum change of up to 20% or approximately 600 mm Hg/s in LVdP/dtmax. DiscussionWe describe a statistical procedure to quantitatively evaluate the acute cardiac effects from studies conducted across six sites and objectively examine the variability and sensitivity that were difficult or impossible to calculate consistently based on previous works. Although this report focuses on the evaluation on LVdP/dtmax, this approach is appropriate for other variables such as heart rate, arterial blood pressure, or variables derived from the ECG.

Evaluation of the Novel easyTEL-D Implantable Digital Telemetry System in Safety Pharmacology: Comparative Results in a Conscious Cardiovascular Canine Model

Evaluation of the Novel easyTEL-D Implantable Digital Telemetry System in Safety Pharmacology: Comparative Results in a Conscious Cardiovascular Canine Model

Initial studies of cardiovascular monitoring feasibility using EndoGear 2, a fully implantable telemetry system in swine model

IntroductionCurrent methodological recommendations for directly translational and clinically relevant models of cardiovascular disease portray large animal models as a mainstay for drug, cell, and gene therapy and for device development and surgical procedure testing. The translational capacity of swine telemetry models has been plagued by an inability to longitudinally assess cardiovascular parameters due to its technological limitations using telemetric instrumentation. Historically, 24‐hour monitoring has required technical staff to physically connect externalized wires which are prone to damage, making the appeal of a fully enclosed automatable data collection system desirable.MethodsWe have performed initial studies to assess cardiovascular parameters employing Transonic EndoGear® 2 (EG2‐Q1S3T‐M25) biotelemetry system on 50kg male domestic swine. At telemeter implantation, a perivascular 2.5 QS flow probe was placed around the left anterior descending coronary artery, 2 ECG leads were attached directly to myocardium, a 3.5F systemic pressure transducer was inserted into the left internal mammary artery and a 7F left ventricular pressure transducer was inserted into the left ventricle via an apical transmural stab. All data were recorded using EMKA IOX software.ResultsAnimals were monitored continuously for 24 hours following the procedure and then for 5 minutes each hour for 1 week subsequently prior to sacrifice. All measurements were within the expected range consistent with previous studies we have performed and animals were able to be reliably monitored for all indicated parameters in real time throughout the monitoring period.ConclusionThese initial studies indicate the feasibility using EndoGear 2 in longitudinal studies monitoring major cardiovascular parameters in untethered and unrestrained swine. The platform enables, for the first time, telemetered monitoring of the coronary artery blood flow using transit time technology.Support or Funding InformationFunded by: R01 HL117620 04

Miniaturized Blood Pressure Telemetry System with RFID Interface

This work deals with the development and characterization of a potentially implantable blood pressure telemetry system, based on an active Radio-Frequency IDentification (RFID) tag, International Organization for Standardization (ISO) 15693 compliant. This approach aims to continuously measure the average, systolic and diastolic blood pressure of the small/medium animals. The measured pressure wave undergoes embedded processing and results are stored onboard in a non-volatile memory, providing the data under interrogation by an external RFID reader. In order to extend battery lifetime, RFID energy harvesting has been investigated. The paper presents the experimental characterization in a laboratory and preliminary in-vivo tests. The device is a prototype mainly intended, in a future engineered version, for monitoring freely moving test animals for pharmaceutical research and drug safety assessment purposes, but it could have multiple uses in environmental and industrial applications.

In-vivo characterization of left-ventricle pressure-volume telemetry system in swine model.

We present in-vivo study related to the use of our implantable RF telemetry system for pressure-volume (PV) cardiac monitoring in a animal subject. We implant a commercial MEMS PV sensor into the subject's heart left-ventricle (LV), while the telemetry system is implanted outside of the heart and connected to the sensor with a 7-microwires tether. The RF telemetry system is suitable for commercial application in medium sized subjects, its total volume of 2.475cm(3) and a weight of 4.0g. Our designed system is 58 % smaller in volume, 44 % in weight and has a 55 % reduction in sampling power over the last reported research in PV telemetry. In-vivo data was captured in both an acute and a freely moving setting over a 24 hour period. We experimentally demonstrated viability of the methodology that includes the surgical procedure and real-time monitoring of the in-vivo data in a freely moving subject. Further improvements in catheter design will improve the data quality and safety of the subject. This real-time implantable technology allows for researchers to quantify cardiac pathologies by extracting real-time pressure-volume loops, wirelessly from within freely moving subjects.

Intermittent electrical stimulation of the right cervical vagus nerve in salt-sensitive hypertensive rats: effects on blood pressure, arrhythmias, and ventricular electrophysiology

Hypertension (HTN) is the single greatest risk factor for potentially fatal cardiovascular diseases. One cause of HTN is inappropriately increased sympathetic nervous system activity, suggesting that restoring the autonomic nervous balance may be an effective means of HTN treatment. Here, we studied the potential of vagus nerve stimulation (VNS) to treat chronic HTN and cardiac arrhythmias through stimulation of the right cervical vagus nerve in hypertensive rats. Dahl salt-sensitive rats (n = 12) were given a high salt diet to induce HTN. After 6 weeks, rats were randomized into two groups: HTN-Sham and HTN-VNS, in which VNS was provided to HTN-VNS group for 4 weeks. In vivo blood pressure and electrocardiogram activities were monitored continuously by an implantable telemetry system. After 10 weeks, rats were euthanized and their hearts were extracted for ex vivo electrophysiological studies using high-resolution optical mapping. Six weeks of high salt diet significantly increased both mean arterial pressure (MAP) and pulse pressure, demonstrating successful induction of HTN in all rats. After 4 weeks of VNS treatment, the increase in MAP and the number of arrhythmia episodes in HTN-VNS rats was significantly attenuated when compared to those observed in HTN-Sham rats. VNS treatment also induced changes in electrophysiological properties of the heart, such as reduction in action potential duration (APD) during rapid drive pacing, slope of APD restitution, spatial dispersion of APD, and increase in conduction velocity of impulse propagation. Overall, these results provide further evidence for the therapeutic efficacy of VNS in HTN and HTN-related heart diseases.

원격 생체 측정 장치를 위한 다중 발신 코일 구동 드라이버 설계

Abstract: Implanted telemetry systems provide the ability to monitor different species of animals while they move within theircages. Species monitored include mice, rats, rabbits, dogs, pigs, primates, sheep, horses, cattle, and others. A miniaturetransmitter implanted in each animal measures one or more parameters. Parameters measured include arterial pressure,intra-pleural pressure, left ventricular pressure, intra-ocular pressure, bladder pressure, ECG, EMG, EEG, EOG, temperature,activity, and other parameters and transmits the data via radio frequency signals to a nearby receiver. Every conventionaldedicated transmitter contains one or more sensors, cpu and battery. Due to the expected life of the battery, the measuring timeis limited. To overcome these problems, electromagnetic inductiv e coupling based wireless power transmission technology usingmultiple transmit coils were proposed, with each coil having a different active area driven by the coil driver. In this research, aparallel resonance based coil driver and serial resonance based coil driver are proposed. From the experiments we see that theparallel coil driver shows better performance under a low impedance and multiple coils configuration. However, the serial coildriver is more efficient for high impedance transmit coils.Keywords: implanted telemetry device, electromagnetic inductive, wireless power transmission technology

다중코일방식에 기초한 원격 생체 정보 측정을 위한 무선전력전송 기술

The implanted telemetry system provides the monitoring of species while they move within their cages. Species monitored include mice, rats, rabbits, dogs, pigs, primates, sheep, horses, cattle, and others. A miniature transmitter implanted in each animal measures one or more parameters. Parameters measured include arterial pressure, intra-pleural pressure, left ventricular pressure, intra-ocular pressure, bladder pressure, ECG, EMG, EEG, EOG, temperature, activity, and other parameters and transmits the data via radio frequency signals to a nearby receiver. Every conventional dedicated transmitter contains one or more sensors, cpu and battery. Due to the expected life of battery, the measuring time is limited. To overcome these problems, electromagnetic inductive coupling based wireless power transmission technology using multiple transmit coils were proposed. Each coil having different active area are driven by the coil driver. In this research, parallel resonance based coil driver was proposed. In addition, the device to detect where the receiver is positioned was proposed. From the experiments we show how to determine the driving condition of coil driver.

Design of a telemetry system based on wireless power transmission for physiological parameter monitoring

An implanted telemetry system for experimental animals with or without anaesthesia can be used to continuously monitor physiological parameters. This system is significant not only in the study of organisms but also in the evaluation of drug efficacy, artificial organs, and auxiliary devices. The system is composed of a miniature electronic capsule, a wireless power transmission module, a data-recording device, and a processing module. An electrocardiograph, a temperature sensor, and a pressure sensor are integrated in the miniature electronic capsule, in which the signals are transmitted in vitro by wireless communication after filtering, amplification, and A/D sampling. To overcome the power shortage of batteries, a wireless power transmission module based on electromagnetic induction was designed. The transmitting coil of a rectangular-section solenoid and a 3D receiving coil are proposed according to stability and safety constraints. Experiments show that at least 150 mW of power could pick up on the load in a volume of Φ10.5 mm × 11 mm, with a transmission efficiency of 2.56%. Vivisection experiments verified the feasibility of the integrated radio-telemetry system.

In-vitro RF characterization of implantable telemetry system

We present the discrete prototype version of our wireless telemetry system architecture, which is suitable for custom IC implementation and intended to eventually retrieve blood pressure and volume...

Acute lower urinary tract dysfunction (LUTD) following traumatic brain injury (TBI) in rats

The aim of this study was to assess experimental traumatic brain injury (TBI)-induced lower urinary tract dysfunction (LUTD) by monitoring systemic and urodynamic parameters using an implantable telemetry system. A single lateral fluid percussion TBI (FP-TBI; 3.4 atm) was administered to 10 female rats. Pressure micro-catheters were implanted in the abdominal aorta and bladder dome for simultaneous data recording. Hemodynamic and urodynamic variables recorded 24 hr before and 24 hr after injury were analyzed and compared. TBI in the acute phase resulted in LUTD affecting bladder emptying, characterized by failure of voiding reflex, high capacity bladder, increased voided volume, prolonged intermicturition intervals, and loss of compliance. The dominant symptom was urinary retention (100%) and incontinence (60%). The effects followed a pattern of initial loss of bladder function followed by either altered recovery of reflex micturition or a period of incontinence. With a moderate injury symptoms were temporary in 90% of animals and permanent in 10% of animals. Injury produced only transient hypertension (≤1 hr) with a maximum systolic pressure of 172.64 ± 14.53 mmHg (70% of animals). The results demonstrate that experimental FP-TBI causes temporary bladder dysfunction that in more severe cases becomes permanent. Telemetry recordings revealed a sequence of events following injury that establishes moderate TBI as a risk factor for neurogenic bladder disorder. Results also suggest a correlation between lateral FP-TBI and incontinence.

Chronic monitoring of brain tissue oxygen in freely moving rats from a fully implanted telemetry system

Chronic monitoring of brain tissue oxygen in freely moving rats from a fully implanted telemetry system