Implantable Telemetry Research Articles

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.

Effects of telemetry implantation surgery on blood pressure and its underlying mechanism

Objective. This study aimed to investigate the effects of radio-telemetry implantation surgery on blood pressure (BP) and renin-angiotensin-aldosterone system (RAAS), calcitonin gene-related peptide (CGRP) and endothelin-1 (ET-1) in rats. Methods: Six spontaneously hypertensive rat (SHRs) and six WKY rats successfully implanted telemetry were used as experimental group, while six SHRs and six Wistar-Kyoto (WKY) rats of comparable age, weight and BP free from implantation surgery were used as normal control group. BP in each group was monitored using the tail cuff method; furthermore, the content of PRA-I, PRA-II, ALD and ET-1, CGRP in plasma was measured with the ELISA. Results: After implantation surgery, there was no general strain difference in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in either SHRs or WKY rats. But there was a significant increase in renin and a suppression of the difference in angiotensin and aldosterone in SHRs and WKY rats. CGRP, ET-1 showed an overall decrease in SHRs and WKY rats. Conclusion: These results indicated that although radio-telemetry is regarded as an efficient and reliable technology for measuring BP, we must pay attention to the influence of the operation itself on BP regulators. After the implantation surgery, decrease in arterial BP or decrease in circulating blood volume might stimulate the secretion of renin, and with the increase of BP and local blood flow, the level of CGRP was decreased. And the decrease of ET-1 may be a kind of protective suppression.

High Intensity Interval Training is Superior to Continuous Training in a Pulmonary Hypertension Rat Model

Exercise appears to have overall benefit in pulmonary arterial hypertension (PAH); however, studies to date indicate little effect on the elevated pulmonary artery pressure (PAP) or RV hypertrophy (RVH) and dysfunction associated with the disease. We investigated if the greater endothelial stimulation of high intensity interval training (HIIT) would provide superior benefit over the more customary prolonged continuous exercise training (CExT) protocol in a rat model of PAH. We further sought to characterize acute PAP responses to HIIT and CExT in a PAH rat. METHODS: Six wks of treadmill training was performed 5x/wk in male Sprague-Dawley rats (250-300g) with monocrotaline- (MCT, 40 mg/kg) induced mild PAH. Training sessions were either HIIT (2 min at ~90% VO2 reserve [VO2R] + 3 min at 30% VO2R, for 5 cycles; n=8), or low intensity CExT (60 min at 50% VO2R; n=7). In an additional rat, telemetric recording of simultaneous PAP and systemic pressures were obtained during HIIT and CExT running, serially at pre- and 2, 4, 6, and 8 wks post-MCT. Values are means±SE. RESULTS: MCT-induced decrement in VO2max was ameliorated by both HIIT and CExT (p≤0.01 vs. sedentary MCT rats, MCT-SED, n=6), and were similar to healthy sedentary controls (CON, n=6). Most importantly, RV systolic pressure (in mmHg) and RVH (ratio of RV to LV+S mass) were lowered (p<0.05) only by HIIT (28.7±2, and 0.32±0.02) and not by CExT (44.1±3, and 0.43±0.01) vs. MCT-SED (40.2±3.2, and 0.41±0.02). Echocardiography performed pre- and post-HIIT also indicated reduced RVH ([INCREMENT] wall thickness 0.11±8 mm) and improved RV function ([INCREMENT] cardiac output 117±28 μl) vs. MCT-SED (0.79±8 mm, and 6±42 μl, p<0.05). RV fibrosis was less only for HIIT (p<0.05 vs. MCT-SED), and no training effect was observed on RV inflammation and apoptosis or pulmonary vascular remodeling. Pulmonary endothelial nitric oxide synthase was increased (p<0.05) only with HIIT, consistent with enhanced endothelial stimulation. Implantable telemetry revealed repeated ‘surging’ of PAP during HIIT running, followed by more pronounced PAP reduction during recovery. CONCLUSIONS: HIIT may be superior to CExT for improving hemodynamics and RV dysfunction in PAH and may be explained by greater sheer-stress mediated vascular endothelial adaptation to HIIT stimulus. Funding: Amer. Heart Assoc. SDG to Brown.

The contributions of cardiac myosin binding protein C and troponin I phosphorylation to β‐adrenergic enhancement of in vivo cardiac function

Key points β‐adrenergic stimulation increases cardiac myosin binding protein C (MyBP‐C) and troponin I phosphorylation to accelerate pressure development and relaxation in vivo, although their relative contributions remain unknown. Using a novel mouse model lacking protein kinase A‐phosphorylatable troponin I (TnI) and MyBP‐C, we examined in vivo haemodynamic function before and after infusion of the β‐agonist dobutamine. Mice expressing phospho‐ablated MyBP‐C displayed cardiac hypertrophy and prevented full acceleration of pressure development and relaxation in response to dobutamine, whereas expression of phosphor‐ablated TnI alone had little effect on the acceleration of contractile function in response to dobutamine. Our data demonstrate that MyBP‐C phosphorylation is the principal mediator of the contractile response to increased β‐agonist stimulation in vivo. These results help us understand why MyBP‐C dephosphorylation in the failing heart contributes to contractile dysfunction and decreased adrenergic reserve in response to acute stress. Abstractβ‐adrenergic stimulation plays a critical role in accelerating ventricular contraction and speeding relaxation to match cardiac output to changing circulatory demands. Two key myofilaments proteins, troponin I (TnI) and myosin binding protein‐C (MyBP‐C), are phosphorylated following β‐adrenergic stimulation; however, their relative contributions to the enhancement of in vivo cardiac contractility are unknown. To examine the roles of TnI and MyBP‐C phosphorylation in β‐adrenergic‐mediated enhancement of cardiac function, transgenic (TG) mice expressing non‐phosphorylatable TnI protein kinase A (PKA) residues (i.e. serine to alanine substitution at Ser23/24; TnIPKA−) were bred with mice expressing non‐phosphorylatable MyBP‐C PKA residues (i.e. serine to alanine substitution at Ser273, Ser282 and Ser302; MyBPCPKA−) to generate a novel mouse model expressing non‐phosphorylatable PKA residues in TnI and MyBP‐C (DBLPKA−). MyBP‐C dephosphorylation produced cardiac hypertrophy and increased wall thickness in MyBPCPKA− and DBLPKA− mice, and in vivo echocardiography and pressure–volume catheterization studies revealed impaired systolic function and prolonged diastolic relaxation compared to wild‐type and TnIPKA– mice. Infusion of the β‐agonist dobutamine resulted in accelerated rates of pressure development and relaxation in all mice; however, MyBPCPKA− and DBLPKA− mice displayed a blunted contractile response compared to wild‐type and TnIPKA– mice. Furthermore, unanaesthesized MyBPCPKA− and DBLPKA− mice displayed depressed maximum systolic pressure in response to dobutamine as measured using implantable telemetry devices. Taken together, our data show that MyBP‐C phosphorylation is a critical modulator of the in vivo acceleration of pressure development and relaxation as a result of enhanced β‐adrenergic stimulation, and reduced MyBP‐C phosphorylation may underlie depressed adrenergic reserve in heart failure.

The Effect of Novel Research Activities on Long-term Survival of Temporarily Captive Steller Sea Lions (Eumetopias jubatus).

Two novel research approaches were developed to facilitate controlled access to, and long-term monitoring of, juvenile Steller sea lions for periods longer than typically afforded by traditional fieldwork. The Transient Juvenile Steller sea lion Project at the Alaska SeaLife Center facilitated nutritional, physiological, and behavioral studies on the platform of temporary captivity. Temporarily captive sea lions (TJs, n = 35) were studied, and were intraperitoneally implanted with Life History Transmitters (LHX tags) to determine causes of mortality post-release. Our goal was to evaluate the potential for long-term impacts of temporary captivity and telemetry implants on the survival of study individuals. A simple open-population Cormack-Jolly-Seber mark-recapture model was built in program MARK, incorporating resightings of uniquely branded study individuals gathered by several contributing institutions. A priori models were developed to weigh the evidence of effects of experimental treatment on survival with covariates of sex, age, capture age, cohort, and age class. We compared survival of experimental treatment to a control group of n = 27 free-ranging animals (FRs) that were sampled during capture events and immediately released. Sex has previously been show to differentially affect juvenile survival in Steller sea lions. Therefore, sex was included in all models to account for unbalanced sex ratios within the experimental group. Considerable support was identified for the effects of sex, accounting for over 71% of total weight for all a priori models with delta AICc <5, and over 91% of model weight after removal of pretending variables. Overall, most support was found for the most parsimonious model based on sex and excluding experimental treatment. Models including experimental treatment were not supported after post-hoc considerations of model selection criteria. However, given the limited sample size, alternate models including effects of experimental treatments remain possible and effects may yet become apparent in larger sample sizes.

Abstract 15949: High Intensity Interval Training is Superior to Continuous Training and Reverses RV Remodeling and Dysfunction in a Rat Model of Pulmonary Hypertension

Exercise appears to have overall benefit in pulmonary arterial hypertension (PAH); however, studies to date indicate little effect on the elevated pulmonary pressure or RV hypertrophy (RVH) and dysfunction associated with the disease. High intensity interval training (HIIT) is reported to be superior to the more customary prolonged continuous exercise training (CExT) protocol for chronic heart failure but has not been tested for PAH. Therefore, we investigated impact of a 6 wk HIIT vs. CExT treadmill program in a monocrotaline rat model of mild PAH (MCT, 40 mg/kg) on indicators of disease progression. Methods: Treadmill training was performed 5x/wk in male Sprague-Dawley MCT rats (250-300g), following a protocol of either HIIT (5 cycles of 2 min at ~90% VO 2 reserve [VO 2 R] + 3 min at 30% VO 2 R; n=8), or low intensity CExT (60 min at 50% VO 2 R; n=7). Statistical analysis was performed by one-way ANOVA. Results: MCT-induced decrements in VO 2 max were ameliorated by both HIIT and CExT (p &lt; 0.01 vs. sedentary MCT rats, MCT-SED, n=6), and were similar to healthy controls (CON, n=6). Most importantly, RV systolic pressure (RVSP, in mmHg; via Millar catheter) and RVH (ratio of RV to LV+S mass) were lowered (p&lt;0.05) only by HIIT (28.7±2, and 0.32±0.02) and not by CExT (44.1±3, and 0.43±0.01) vs. MCT-SED (40.2±3.2, and 0.41±0.02). Cardiac output (Δ from baseline in μl, via RV echocardiography) was also improved by HIIT (117±28) vs. MCT-SED (6±42, p=0.04). Additional hemodynamic recordings during running, via novel implantable telemetry (DSI), were obtained serially at pre- and 2, 4, 6, and 8 wks post-MCT, and revealed ‘surges’ in RVSP during HIIT, vs. a steady RVSP pattern during CExT. Pulmonary eNOS (per immunoblotting) was increased (p&lt;0.05) with HIIT, consistent with greater endothelial stimulation. Conclusions: HIIT is superior to CExT for improving hemodynamics and RV remodeling and dysfunction in MCT rats and warrants further investigation in other models and in patients. More favorable outcomes may be explained by greater sheer-stress mediated vascular endothelial adaptation to HIIT stimulus, or lower cumulative training-induced RV wall stress with the briefer HIIT session duration.

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.

Novel assessment of haemodynamic kinetics with acute exercise in a rat model of pulmonary arterial hypertension

What is the central question of this study? The acute effect of exercise at moderately high intensity on already-elevated pulmonary arterial pressures and right ventricular wall stress in a rat model of pulmonary arterial hypertension (PAH) is unknown. What is the main finding and its importance? We show, for the first time, that in a rat model of PAH, exercise induces an acute reduction in pulmonary artery pressure associated with lung endothelial nitric oxide synthase activation, without evidence of acute right ventricular inflammation or myocyte apoptosis. Haemodynamic measures obtained with traditional invasive methodology as well as novel implantable telemetry reveal an exercise-induced 'window' of pulmonary hypertension alleviation, supporting future investigations of individualized exercise as therapy in PAH. Exercise improves outcomes of multiple chronic conditions, but controversial results, including increased pulmonary artery (PA) pressure, have prevented its routine implementation in pulmonary arterial hypertension (PAH), an incurable disease that drastically reduces exercise tolerance. Individualized, optimized exercise prescription for PAH requires a better understanding of disease-specific exercise responses. We investigated the acute impact of exercise on already-elevated PA pressure and right ventricular (RV) wall stress and inflammation in a rat model of PAH (PAH group, n = 12) induced once by monocrotaline (50 mg kg(-1) , i.p.; 2 weeks), compared with healthy control animals (n = 8). Single bouts of exercise consisted of a 45 min treadmill run at 75% of individually determined aerobic capacity (V̇O2max). Immediately after exercise, measurements of RV systolic pressure and systemic pressure were made via jugular and carotid cannulation, and were followed by tissue collection. Monocrotaline induced moderate PAH, evidenced by RV hypertrophy, decreased V̇O2max, PA muscularization, and RV and skeletal muscle cytoplasmic glycolysis detected by increased expression of glucose transporter-1. Acute exercise normalized the monocrotaline-induced elevation in RV systolic pressure and augmented pulmonary endothelial nitric oxide synthase activation, without evidence of increased RV inflammation or apoptosis. Real-time recordings of pulmonary and systemic pressures during and after single bouts of exercise made using novel implantable telemetry in the same animal for up to 11 weeks after monocrotaline (40 mg kg(-1) ) corroborated the finding of acute PA pressure decreases with exercise in PAH. The PA pressure-lowering effects of individualized exercise associated with RV-neutral effects and increases in vasorelaxor signalling encourage further development of optimized exercise regimens as adjunctive PAH therapy.

High fidelity biopotential recordings in mice using a novel telemetry implant

We have developed a fully implantable telemetry device for use in mice.The telemeter is able to measure biopotential signals (EEG, EMG, ECG) at a sampling rate of 2000 Hz. The device has a volume of 1.45 cc with a unique contour design for subcutaneous implantation in mice over 20 gm in weight. A novel aspect to the device is that it contains no battery. Power to run the telemeter is provided by a wireless power pad placed under the cage of the animal. This provides continual operation of the telemeter (&gt;90% data collection in a 24 hour period) during a range of normal animal behaviours. We have assessed the ability of this device to record biopotential signals for up to 3 months. We believe this technology offers new experimental paradigms to be explored.

Detailed analysis of the African green monkey model of Nipah virus disease.

Henipaviruses are implicated in severe and frequently fatal pneumonia and encephalitis in humans. There are no approved vaccines or treatments available for human use, and testing of candidates requires the use of well-characterized animal models that mimic human disease. We performed a comprehensive and statistically-powered evaluation of the African green monkey model to define parameters critical to disease progression and the extent to which they correlate with human disease. African green monkeys were inoculated by the intratracheal route with 2.5×104 plaque forming units of the Malaysia strain of Nipah virus. Physiological data captured using telemetry implants and assessed in conjunction with clinical pathology were consistent with shock, and histopathology confirmed widespread tissue involvement associated with systemic vasculitis in animals that succumbed to acute disease. In addition, relapse encephalitis was identified in 100% of animals that survived beyond the acute disease phase. Our data suggest that disease progression in the African green monkey is comparable to the variable outcome of Nipah virus infection in humans.

Central Sympathetic Activation and Arrhythmogenesis during Acute Myocardial Infarction: Modulating Effects of Endothelin-B Receptors.

Sympathetic activation during acute myocardial infarction (MI) is an important arrhythmogenic mechanism, but the role of central autonomic inputs and their modulating factors remain unclear. Using the in vivo rat-model, we examined the effects of clonidine, a centrally acting sympatholytic agent, in the presence or absence of myocardial endothelin-B (ETB) receptors. We studied wild-type (n = 20) and ETB-deficient rats (n = 20) after permanent coronary ligation, with or without pretreatment with clonidine. Cardiac rhythm was continuously recorded for 24 h by implantable telemetry devices, coupled by the assessment of autonomic and heart failure indices. Sympathetic activation and arrhythmogenesis were more prominent in ETB-deficient rats during the early phase post-ligation. Clonidine improved these outcomes throughout the observation period in ETB-deficient rats, but only during the delayed phase in wild-type rats. However, this benefit was counterbalanced by atrioventricular conduction abnormalities and by higher incidence of heart failure, the latter particularly evident in ETB-deficient rats. Myocardial ETB-receptors attenuate the arrhythmogenic effects of central sympathetic activation during acute MI. ETB-receptor deficiency potentiates the sympatholytic effects of clonidine and aggravates heart failure. The interaction between endothelin and sympathetic responses during myocardial ischemia/infarction and its impact on arrhythmogenesis and left ventricular dysfunction merits further investigation.

Abstract 19492: Novel Assessment of Pulmonary and Systemic Pressures During Treadmill Testing via Implantable Telemetry in a Rat Model of Pulmonary Arterial Hypertension

Objectives: 1) To determine if pulmonary arterial pressures (PAP) may be measured simultaneously with systemic blood pressures (BP) during exercise testing in laboratory rats using implantable telemetry; and 2) To determine the relationship of exercise intensity to acute PAP exercise responses over the course of PAH development. Methods: A specialized implantable transmitter (Data Sciences International); via telemetry following thoracotomy with right ventricular (RV) and abdominal aortic catheter positioning, respectively enabled simultaneous systolic, diastolic and mean PAP and BP recordings. Following recovery, an incremental treadmill test measured maximal aerobic capacity (VO 2 max) via analysis of expired gases. Steady state exercise testing was then performed for 3 different submaximal relative intensities: 50, 75, and 90% VO 2 max. Pressures were recorded during each test, as well as pre- and post- exercise. At 2.5 weeks following monocrotaline (MCT, 40 mg/kg) administration (mild PH) and 7 weeks post-MCT (advanced PH), VO 2 max and steady-state exercise tests were repeated. Results: Compared to pre-MCT, at 2.5 weeks post-MCT systolic PAP increased from 25 to 41 mmHg at rest; from 105 to 117 mmHg at peak exercise; and from 40 to 58 mmHg, 46 to 65 mmHg, and 55 to 75 mmHg during running at 50, 75, and 90% VO 2 max, respectively. At 7 weeks post-MCT, PAP further increased at rest (to 59 mmHg), and during steady state running (to 69, 70, and 73 mmHg, at 50, 75, and 90% VO 2 max, respectively). During recovery from steady state exercise, the fall in PAP occurred more rapidly post-MCT, bringing PAP to even lower than resting from 10 min to 2h into recovery. Conclusions: Using implantable telemetry we have accomplished dual pressure recordings during serial exercise tests before and after PAH induction. The rise in PAP relative to exercise intensity is steeper in PAH but is accompanied by a post-exercise window of normalized PAP, which may be attributed to pronounced acute pulmonary endothelial activation. Future work will investigate how these acute effects translate to wall stress and RV remodeling with chronic exercise training and may allow for optimized exercise prescription for patients affected with PAH.

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...

Sleep electroencephalographic characteristics of the Cynomolgus monkey measured by telemetry.

Cynomolgus monkeys are widely used as models of diseases and in pre-clinical studies to assess the impact of new pharmacotherapies on brain function and behaviour. However, the time course of electroencephalographic delta activity during sleep, which represents the main marker of sleep intensity associated with recovery during sleep, has never been described in this non-human primate. In this study, telemetry implants were used to record one spontaneous 24-h sleep-wake cycle in four freely-moving Cynomolgus monkeys, and to quantify the time course of electroencephalographic activity during sleep using spectral analysis. Animals presented a diurnal activity pattern interrupted by short naps. During the dark period, most of the time was spent in sleep with non-rapid eye movement sleep/rapid eye movement sleep alternations and sleep consolidation profiles intermediate between rodents and humans. Deep non-rapid eye movement sleep showed a typical predominance at the beginning of the night with decreased propensity in the course of the night, which was accompanied by a progressive increase in rapid eye movement sleep duration. Spectral profiles showed characteristic changes between vigilance states as reported in other mammalian species. Importantly, delta activity also followed the expected time course of variation, showing a build-up with wakefulness duration and dissipation across the night. Thus, Cynomolgus monkeys present typical characteristics of sleep architecture and spectral structure as those observed in other mammalian species including humans, validating the use of telemetry in this non-human primate model for translational sleep studies.

In vivo telemetric determination of shear and axial loads on a regenerative cartilage scaffold following ligament disruption

Recent interest in repair of chondral and osteochondral cartilage defects to prevent osteoarthritis caused by ligament disruption has led to the research and development of biomimetic scaffolds combined with cell-based regeneration techniques. Current clinical focal defect repair strategies have had limited success. New scaffold-based approaches may provide solutions that can repair extensive damage and prevent osteoarthritis. This study utilized a novel scaffold design that accommodated strain gauges for shear and axial load monitoring in the canine stifle joint through implantable telemetry technology. Loading changes induced by ligament disruption are widely implicated in the development of injury-related osteoarthritis. Seeding the scaffold end with progenitor cells resulted in higher shear stress than without cell seeding and histology showed significantly more bone and cartilage formation. Biomechanically, the effect of transecting the anterior cruciate ligament was a significant reduction in braking load in shear, but no change axially, and conversely a significant reduction in push-off load axially, but no change in shear. This is the first study to report shear loads measured directly in knee joint tissue. Further, advances of these measurement techniques are critical to developing improved regeneration strategies and personalizing reliable rehabilitation protocols.

Evaluation of the sensitivity of a new fully implantable telemetry device and the importance of simultaneously measuring cardiac output and left ventricular pressure

IntroductionThe absence of drug-induced changes in heart rate (HR), aortic pressure (AOP) and ECG, the minimum endpoints suggested in ICH S7A, does not necessarily indicate the absence of cardiovascular (CV) pharmacodynamic activity. This potential pitfall can be avoided by prospectively incorporating “follow-up” endpoints in initial evaluations made possible by the advent of new telemetry implants capable of also measuring changes in cardiac output (CO) and left ventricular pressure (LVP). The purpose of this study was (1) to evaluate the sensitivity of a new, fully implantable telemetry device, and (2) to highlight the importance of the device to simultaneously measure cardiac output and left ventricular pressure in order to adequately evaluate the full potential for a drug to impact global cardiovascular function. Methods4 dogs were instrumented with Konigsberg Instruments, Inc. (KI) TU7/T27H series fully implantable telemetry device and recovered for >8weeks. Sotalol (8mg/kg), milrinone (0.2mg/kg), hydralazine (0.2mg/kg) and control were administered 1week apart. Data were collected for 1h pre- and 24h post-treatment and time-averaged to fully characterize the a priori pharmacodynamic effects of interest for each drug. This included PR and QTci (sotalol); HR, AOP and LVP (milrinone); HR, AOP, CO and systemic vascular resistance (SVR) (hydralazine). ResultsExpected changes in CV parameters were observed following all drugs with the following detection sensitivities: PR and QTci of 4ms and 3ms, respectively (sotalol); AOP and LVP dP/dt+max of 5mmHg and 232mmHg/s, respectively (milrinone); HR, CO and SVR of 11bpm, 0.302l/min and 5mmHg∗min/l, respectively (hydralazine). DiscussionKI TU7/T27H implant detects drug-induced CV changes with statistical significance using a standard, four-subject design. The ability of the TU7/T27H to also measure CO and LVP allowed for full characterization of the CV impact of hydralazine and milrinone, which could have been misinterpreted/missed altogether if these drugs were novel and the endpoints evaluated were prospectively limited to the minimum suggested in ICH S7A.

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.

The short-term effects of antenna insulation thickness on path losses in wireless telemetry implants at microwave frequencies

Various physiological parameters can be monitored non-invasively using wireless biotelemetry links. The development of sophisticated ultra low power consuming transceivers allows the transmission of large amounts of data from the inside of the body to an external receiver in real time at microwave frequencies.Antenna impedance matching is crucial for obtaining an acceptable propagation link budget in a wireless telemetry link. The dielectric properties of biological tissue induce detuning to transceiver antennas when implanted into the body. To counteract detuning problems, implant antennas are coated with biocompatible insulating material. The study investigates the propagation losses of a wireless communication link at different insulation thicknesses of medical grade silicone in the Industrial-Scientific-Medical (ISM) radio band at 2.45 GHz. The wireless link consisted of an implantable unit which was placed between two pads of tissue substitute material and an external receiver which was connected to a laptop. Predefined data packets were transmitted from the implant, the received packets were analyzed, packet errors and packet losses were logged and the received signal strength indicator values (RSSI) were recorded. Our results showed that the mean RSSI values of insulated transmitter antennas - embedded in tissue equivalent material - provide more safety distance to critical receiver sensitivity level than uncoated antennas.The conducted measurements let us conclude that with increasing thickness of the insulation layer, the antenna becomes less sensitive to detuning by adjacent tissue substitute material. Therefore tuned antennas are less influenced by the surrounding tissue after implantation.

The short-term effects of antenna insulation thickness on path losses in wireless telemetry implants at microwave frequencies

Various physiological parameters can be monitored non-invasively using wireless biotelemetry links. The development of sophisticated ultra low power consuming transceivers allows the transmission of large amounts of data from the inside of the body to an external receiver in real time at microwave frequencies.Antenna impedance matching is crucial for obtaining an acceptable propagation link budget in a wireless telemetry link. The dielectric properties of biological tissue induce detuning to transceiver antennas when implanted into the body. To counteract detuning problems, implant antennas are coated with biocompatible insulating material. The study investigates the propagation losses of a wireless communication link at different insulation thicknesses of medical grade silicone in the Industrial-Scientific-Medical (ISM) radio band at 2.45 GHz. The wireless link consisted of an implantable unit which was placed between two pads of tissue substitute material and an external receiver which was connected to a laptop. Predefined data packets were transmitted from the implant, the received packets were analyzed, packet errors and packet losses were logged and the received signal strength indicator values (RSSI) were recorded. Our results showed that the mean RSSI values of insulated transmitter antennas - embedded in tissue equivalent material - provide more safety distance to critical receiver sensitivity level than uncoated antennas.The conducted measurements let us conclude that with increasing thickness of the insulation layer, the antenna becomes less sensitive to detuning by adjacent tissue substitute material. Therefore tuned antennas are less influenced by the surrounding tissue after implantation.