Pulmonary Veins Function as Echo Chambers in Persistent Atrial Fibrillation: Circuitous Re-Entry Generates Outgoing Wavefronts.

BACKGROUND: Although the substrate in persistent atrial fibrillation (PeAF) is not limited to the pulmonary veins (PVs), PV isolation (PVI) remains the cornerstone ablation strategy. OBJECTIVES: The aim of this study was to describe the mechanism of outgoing wavefronts (WFs) originating in the PV sleeves during PeAF. METHODS: Eleven patients presenting for first-time PeAF ablation were recruited (mean age 63.1 ± 10.9 years, 91% men). A 64-electrode catheter (Constellation; 38 mm) was positioned within the PV under fluoroscopic guidance. An inverse mapping technique was used to reconstruct unipolar atrial electrograms on the PV surface, and the resulting phase maps were used to identify incoming and outgoing WFs at the PV junction and to classify focal and re-entrant activity within the PV sleeves. RESULTS: During PeAF, the PVs gave rise to outgoing WFs with a frequency of 3.7 s-1 (Q1-Q3: 3.4-5.4 s-1) compared with 3.6 s-1 (Q1-Q3: 2.8-4.2 s-1) for incoming WFs. Circuitous macroscopic re-entry was the dominant mechanism driving outgoing WFs (frequency of re-entry 2.7 s-1 [Q1-Q3: 2.0-3.3 s-1] compared with focal activity 1.4 s-1 [Q1-Q3: 1.1-1.5 s-1]; P < 0.006). This was initiated by incoming WFs in 80% of cases. Consecutive focal activation from the same location was infrequent (10.0% ± 6.6%, n = 10). Rotors ≥360° were never observed. The median ratio (R) of outgoing to incoming WF frequency was 1.14 (Q1-Q3: 0.84-1.75), with R > 1 in 6 of 11 PVs. CONCLUSIONS: Electric activity generated by PV sleeves during PeAF is due mainly to circuitous re-entry initiated by incoming waves, frequently with R > 1. That is, the PVs act less as drivers of atrial fibrillation than as "echo chambers" that sustain and amplify fibrillatory activity.

A pneumatic reconfigurable socket for transtibial amputees.

Many transtibial amputees rate the fit between their residual limb and prosthetic socket as the most critical factor in satisfaction with using their prosthesis. This study aims to address the issue of prosthetic socket fit by reconfiguring the socket shape at the interface of the residual limb and socket. The proposed reconfigurable socket shifts pressure from sensitive areas and compensates for residual limb volume fluctuations, the most important factors in determining a good socket fit. Computed tomography scan images are employed to create the phantom limb of an amputee and to manufacture the reconfigurable socket. The performance of the reconfigurable socket was evaluated both experimentally and numerically using finite element modelling. The study showed that the reconfigurable socket can reduce interface pressure at targeted areas by up to 61%.

Non-Contact Intracardiac Potential Mapping Using Mesh-Based and Meshless Inverse Solvers.

Atrial fibrillation (AF) is the most common cardiac dysrhythmia and percutaneous catheter ablation is widely used to treat it. Panoramic mapping with multi-electrode catheters has been used to identify ablation targets in persistent AF but is limited by poor contact and inadequate coverage of the left atrial cavity. In this paper, we investigate the accuracy with which atrial endocardial surface potentials can be reconstructed from electrograms recorded with non-contact catheters. An in-silico approach was employed in which "ground-truth" surface potentials from experimental contact mapping studies and computer models were compared with inverse potential maps constructed by sampling the corresponding intracardiac field using virtual basket catheters. We demonstrate that it is possible to 1) specify the mixed boundary conditions required for mesh-based formulations of the potential inverse problem fully, and 2) reconstruct accurate inverse potential maps from recordings made with appropriately designed catheters. Accuracy improved when catheter dimensions were increased but was relatively stable when the catheter occupied >30% of atrial cavity volume. Independent of this, the capacity of non-contact catheters to resolve the complex atrial potential fields seen in reentrant atrial arrhythmia depended on the spatial distribution of electrodes on the surface bounding the catheter. Finally, we have shown that reliable inverse potential mapping is possible in near real-time with meshless methods that use the Method of Fundamental Solutions.

Intracardiac Inverse Potential Mapping Using the Method of Fundamental Solutions.

Introduction: Atrial fibrillation (AF) is the most prevalent cardiac dysrhythmia and percutaneous catheter ablation is widely used to treat it. Panoramic mapping with multi-electrode catheters can identify ablation targets in persistent AF, but is limited by poor contact and inadequate coverage. Objective: To investigate the accuracy of inverse mapping of endocardial surface potentials from electrograms sampled with noncontact basket catheters. Methods: Our group has developed a computationally efficient inverse 3D mapping technique using a meshless method that employs the Method of Fundamental Solutions (MFS). An in-silico test bed was used to compare ground-truth surface potentials with corresponding inverse maps reconstructed from noncontact potentials sampled with virtual catheters. Ground-truth surface potentials were derived from high-density clinical contact mapping data and computer models. Results: Solutions of the intracardiac potential inverse problem with the MFS are robust, fast and accurate. Endocardial surface potentials can be faithfully reconstructed from noncontact recordings in real-time if the geometry of cardiac surface and the location of electrodes relative to it are known. Larger catheters with appropriate electrode density are needed to resolve complex reentrant atrial rhythms. Conclusion: Real-time panoramic potential mapping is feasible with noncontact intracardiac catheters using the MFS. Significance: Accurate endocardial potential maps can be reconstructed in AF with appropriately designed noncontact multi-electrode catheters.

A Capacitive Pressure Sensor Interface IC with Wireless Power and Data Transfer.

This paper presents a capacitive pressure sensor interface circuit design in 180 nm XH018 CMOS technology for an implantable capacitive pressure sensor, which has a wireless power supply and wireless data transfer function. It integrates full-bridge rectifiers, shorting control switches, low-dropout regulators, bandgap references, analog front end, single slope analog to digital converter (ADC), I2C, and an RC oscillator. The low-dropout regulators regulate the wireless power supply coming from the rectifier and provide a stable and accurate 1.8 V DC voltage to other blocks. The capacitance of the pressure sensor is sampled to a discrete voltage by the analog front end. The single slope ADC converts the discrete voltage into 11 bits of digital data, which is then converted into 1 kbps serial data out by the I2C block. The "1" of serial data is modulated to a 500 kHz digital signal that is used to control the shorting switch for wireless data transfer via inductive back scatter. This capacitive pressure sensor interface IC has a resolution of 0.98 mmHg (1.4 fF), average total power consumption of 7.8 mW, and ±3.2% accuracy at the worst case under a -20 to 80 °C temperature range, which improves to ±0.86% when operated between 20 and 60 °C.

Injection Molded Liquid Crystal Polymer Package for Chronic Active Implantable Devices With Application to an Optogenetic Stimulator.

Implanted electronics require protection from the body's fluids to avoid moisture induced failure. This study presents an injection molded liquid crystal polymer (LCP) package to protect active implantable devices for chronic applications, such as in optogenetic research. The technology is applied and assessed through a custom package for a fully implantable optogenetic stimulation system, built on a versatile telemetry system that can incorporate additional stimulating and recording channels. An adapted quasi-steady state model predicts the lifetime of an enclosure, where the definition of the lifetime is the time before the internal relative humidity (RH) reaches a time constant, or 63%RH, a conservative limit to minimize the risk of corrosion. The lifetime of the LCP optogenetic device is 94 days, and can be extended to 326 days with the inclusion of 5% w/v silica gel desiccant. Samples of the LCP optogenetic device containing humidity sensors testing in saline at 38 °C support the RH change predictions. Desiccants inside the implant enclosure can store permeating moisture and prolong the life expectancy of LCP-based implants to years or decades. The results of this study demonstrates the feasibility of providing reliable protection for chronic optogenetic implants, and the technology can be transferred to other applications as an easily-manufactured, cost-effective, radiofrequency compatible alternative to hermetic packaging for chronic studies.

Pulse-Width Modulation of Optogenetic Photo-Stimulation Intensity for Application to Full-Implantable Light Sources.

Optogenetics allows control of neuronal activity with unprecedented spatiotemporal precision, and has enabled both significant advances in neuroscience and promising clinical prospects for some neurological, cardiac, and sensory disorders. The ability to chronically stimulate light-sensitive excitable cells is crucial for developing useful research tools and viable long-term treatment strategies. Popular optogenetic stimulation devices often rely on bench-top light-sources tethered via an optical fibre to the research animal, or significant componentry protruding externally from animal. These approaches are prone to infection, vulnerable to damage and restrict the experimental approaches that can be conducted. An ideal optogenetic stimulator would be contained entirely within the animal and provide precisely controlled optical output. However, existing prototypes of fully implantable devices rely on amplitude tuning of wireless power, which can vary strongly with environmental conditions. Here we show that pulse-width modulation (PWM) of the intensity of a light-emitting diode (LED) can enable control of photo-stimulation intensity equivalent to direct amplitude modulation. This result has significant implications for fully implantable light delivery tools, as PWM can be implemented with simple and miniaturized circuit architectures. We have modified a telemeter device previously developed by our group to include a small form-factor LED capable of generating sufficient optical power with manageable electrical power requirements and minimal heat generation. We have tested key device components in an in vitro mouse brain slice preparation and shown that pulse-width-modulation is an alternative method to modulate photo-stimulation intensity using a miniature circuit and providing easy control.

New multimodal data obtained in-vivo from a single ultra-miniature transducer.

Recent advances in multimodal sensing technology and sensor miniaturization technologies are paving the way for a new era in physiological measurement. Traditional approaches have integrated several transducers on a single silicon chip or packaged several sensing elements within a biocompatible catheter. Thermal and electrical cross-talk between sensors, time-lag between parallel measurements, lower yields associated with the increased complexity, and restrictions on the minimum size are challenges presented by these approaches. We present an alternative method which enables simultaneous measurement of temperature, pressure and heart rate to be obtained from a single ultra-miniature solid-state transducer. For the first time multimodal data were obtained from the sensor located within the abdominal aortas of five rats. The catheter-tip sensor interfaces with a fully implanted and inductively powered telemetry device capable of operating for the lifetime of the animal. Results of this study demonstrate good agreement between the core-temperature measurement from the catheter-tip sensor and the reference sensor with mean difference between the two sensors of 0.03 °C ± 0.02 °C (n = 5, 7 days). Real-time data obtained in the undisturbed rat, revealed fluctuations associated with the rest-activity cycle, in temperature, mean arterial pressure and heart rate. The stress response was shown to elicit an elevation in the core temperature of 1.5 °C. This was heralded by an elevation in mean arterial pressure of 35 mmHg and heart rate of 160 bpm. Obtaining multiple parameters from a single transducer goes a considerable way towards overcoming challenges of the prior art.

MRI interactions of a fully implantable pressure monitoring device.

PURPOSE: To investigate the potential patient risk and interactions between a prototype implantable pressure monitoring device and a 3T clinical magnetic resonance imaging (MRI) machine to guide device design towards MR Conditional safety approval. MATERIALS AND METHODS: The pressure monitor device contained a catheter-mounted piezo-resistive pressure sensor, rechargeable battery, wireless communication system, and inductive pickup coil. Standard testing methods were used to guide experiments to investigate static field induced force and torque, radiofrequency (RF)-induced heating, image artifacts, and the MR's effect on device function. The specific clinical application of intracranial pressure monitoring was considered. RF-induced heating experiments were supported by numerical modeling of the RF body coil, the device, and experimental phantom. RESULTS: Sensing catheter lead length and configuration was an important component of the device design. A short 150 mm length catheter produced a heating effect of less than 2°C and a long 420 mm length catheter caused heating of 7.2°C. Static magnetic field interactions were below standard safety risk levels and the MR did not interfere with device function; however, artifacts have the potential to interfere with image quality. CONCLUSION: Investigation of MR interactions at the prototype stage provides useful implantable device design guidance and confidence that an implantable pressure monitor may be able to achieve MR Conditional safety approval.

Clinical evaluation of a high-fidelity wireless intravaginal pressure sensor.

INTRODUCTION AND HYPOTHESIS: A wireless intravaginal pressure sensor (IVPS) has been developed to quantify abdominal pressure (P(abd)) changes during exercise and activities of daily living to guide post-operative advice given to women. In this pilot study, we aimed to compare IVPS performance, comfort, retention, and acceptability to a standard fluid-filled intrarectal pressure catheter currently used to measure P(abd) during routine urodynamics. METHODS: A Life-Tech 3-mm urodynamic intrarectal catheter and IVPS were inserted concurrently in volunteers attending a urodynamics clinic. The IVPS was positioned above the levator plate and the intrarectal catheter positioned in routine fashion well above the anal sphincter. Routine urodynamics was undertaken, with women asked to perform star jumps if coughing or Valsalva did not invoke leakage. Subjects rated device comfort using a visual analogue scale (0-10). Repeated measures Bland-Altman analysis determined level of agreement (LOA) between the two devices for peak pressures for each activity. RESULTS: Twenty-seven women were recruited, 67% of the participants preferred the IVPS, 18% the intrarectal catheter, while 15% had no preference. Mean comfort score was 0.9 ± 1.7 and 2.1 ± 2.6 (p = 0.049) for the IVPS and intrarectal catheter respectively. Bland-Altman analysis demonstrated minimal bias for cough and Valsalva, however LOA were wide. Differences were more prominent during star jumps where rapid dynamic pressure changes occurred. CONCLUSIONS: The IVPS had a higher comfort score and was well retained. The LOA between the two systems was moderate, but the high sampling rate and lower susceptibility to motion artefacts of the IVPS may provide more accurate information that will be important clinically.

Chronic measurement of left ventricular pressure in freely moving rats.

Measurements of left ventricular pressure (LVP) in conscious freely moving animals are uncommon, yet could offer considerable opportunity for understanding cardiovascular disease progression and treatment. The aim of this study was to develop surgical methods and validate the measurements of a new high-fidelity, solid-state pressure-sensor telemetry device for chronically measuring LVP and dP/dt in rats. The pressure-sensor catheter tip (2-Fr) was inserted into the left ventricular chamber through the apex of the heart, and the telemeter body was implanted in the abdomen. Data were measured up to 85 days after implant. The average daytime dP/dt max was 9,444 ± 363 mmHg/s, ranging from 7,870 to 10,558 mmHg/s (n = 7). A circadian variation in dP/dt max and heart rate (HR) was observed with an average increase during the night phase in dP/dt max of 918 ± 84 mmHg/s, and in HR of 38 ± 3 bpm. The ß-adrenergic-agonist isoproterenol, ß1-adrenergic agonist dobutamine, Ca(2+) channel blocker verapamil, and the calcium sensitizer levosimendan were administered throughout the implant period, inducing dose-dependent time course changes and absolute changes in dP/dt max of -6,000 to +13,000 mmHg/s. The surgical methods and new technologies demonstrated long-term stability, sensitivity to circadian variation, and the ability to measure large drug-induced changes, validating this new solution for chronic measurement of LVP in conscious rats.

A fully implantable telemetry system for the chronic monitoring of brain tissue oxygen in freely moving rats.

The ability to monitor tissue oxygen concentration in a specific region of the brain in a freely moving animal could provide a new paradigm in neuroscience research. We have developed a fully implantable telemetry system for the continuous and chronic recording of brain tissue oxygen (PO(2,BR)) in conscious animals. A telemetry system with a sampling rate of 2kHz was combined with a miniaturized potentiostat to amperiometrically detect oxygen concentration with carbon paste electrodes. Wireless power was employed to recharge the telemeter battery transcutaneously for potential lifetime monitoring. Rats were implanted with the telemeter in the peritoneal cavity and electrodes stereotaxically implanted into the brain (striatum or medulla oblongata). While the animals were living in their home cages the sensitivity to changes in oxygen was validated by repeatedly altering the inspired oxygen (10%, 100%, respectively) or a pharmacological stimulus (carbonic anhydrase inhibitor: acetazolamide 50mg/kg IP). Basal level of PO(2,BR) was monitored for 3weeks and showed good overall stability and good correlation to movement such as grooming. During hypoxia, PO(2,BR) decreased significantly by -51%±2% from baseline, whereas it increased by 34%±3% during hyperoxia. Following the systemic administration of acetazolamide, PO(2,BR) increased by 38%±4%. We propose this new technology provides a robust method to measure changes in oxygen concentration in specific areas of the brain, in conscious freely moving rats. The ability to track long term changes with disease progression or drug treatment may be enabled.

A high bandwidth fully implantable mouse telemetry system for chronic ECG measurement.

We report on the development of a novel system that enables the wireless transmission of high-bandwidth physiological data from a freely moving mouse. The system employs inductive power transfer (IPT) to continuously power a battery-less transmitter using an array of overlapping planar coils placed under the animal. This arrangement provides a minimum of 20 mW at all locations and orientations across the mouse cage by selecting a coil which will sufficiently power the transmitter. Coil selection is performed by feedback control across the 2.4 GHz wireless link. A device was constructed utilizing this novel IPT system and was used to capture high-fidelity electrocardiogram (ECG) signal sampled at 2 kHz in mice. Various attributes of the ECG signal such as QT, QRS, and PR intervals could be obtained with a high degree of accuracy. This system potentially provides lifetime continuous high bandwidth measurement of physiological signals from a fully implanted telemeter in a freely moving mouse.

Reactive component selection for TET powered medical devices.

Transcutaneous energy transfer (TET) is capable of supplying power across the skin to implantable devices and avoids the risk of infection associated with wires passing through the skin. These systems rely on a high frequency magnetic field to overcome the relatively low coupling between a coil located outside the body, and a coil implanted within the body. This paper introduces a new optimisation procedure to choose tuning capacitors that minimises the amount of power dissipated in the power transfer coils of an implantable TET system. The frequency of operation is determined by the selection of the resonant reactive components. By analysing the overall circuit impedance it is possible to observe that a Zero Voltage Switched TET system may dissipate different amounts of power in the power transfer coils while delivering the same amount of power. In this study an objective function was developed to determine the best configuration of resonant capacitors for any particular set of TET coils in order to minimize power loss. The method is used to find the value of the resonant capacitors for a system delivering 15 W over a coupling range of k=0.1 to 0.55 (corresponding to a separation of up to 20mm).

A novel low temperature transcutaneous energy transfer system suitable for high power implantable medical devices: performance and validation in sheep.

Transcutaneous energy transfer (TET) systems use magnetic fields to transfer power across the skin without direct electrical connectivity. This offers the prospect of lifetime operation and overcomes risk of infection associated with wires passing through the skin. Previous attempts at this technology have not proved suitable due to poor efficiency, large size, or tissue damage. We have developed a novel approach utilizing frequency control that allows for wide tolerance in the alignment between internal and external coils for coupling variations of 10 to 20 mm, and relatively small size (50 mm diameter, 5 mm thickness). Using a sheep experimental model, the secondary coil was implanted under the skin in six sheep, and the system was operated to deliver a stable power output to a 15 W load continuously over 4 weeks. The maximum surface temperature of the secondary coil increased by a mean value of 3.4 +/- 0.4 degrees C (+/-SEM). The highest absolute mean temperature was 38.3 degrees C. The mean temperature rise 20 mm from the secondary coil was 0.8 +/- 0.1 degrees C. The efficiency of the system exceeded 80% across a wide range of coil orientations. Histological analysis revealed no evidence of tissue necrosis or damage after four weeks of operation. We conclude that this technology is able to offer robust transfer of power to implantable devices without excess heating causing tissue damage.

Frequency response of implantable blood pressure telemetry systems.

1. Measurement of blood pressure via telemetry in a variety of animal species has become an indispensable part of cardiovascular physiology, drug development and safety pharmacology. 2. These telemetry systems use fluid-filled catheters, which differ from commonly encountered indwelling catheters by virtue of their short length, high durometer, variable inner diameter and the use of a gel interface at the distal tip. 3. Despite the widespread use of blood pressure telemetry, there is little information describing the frequency response of these systems. The frequency response is of importance because it determines how well the waveform dynamics, such as pulse pressure, are captured. 4. For this reason, we measured the frequency responses of commonly used telemeters manufactured by Data Sciences International (St Paul, MN, USA; namely PA-C10, PA-C40 and PA-D70) and Telemetry Research (TR43P). The mean (+/- SEM) -3 dB frequencies measured for the PA-C10, PA-C40, PA-D70 and TR43P telemeters were 57 +/- 2 Hz, 40 +/- 6 Hz, 32 +/- 2 Hz and 173 +/- 3 Hz, respectively. 5. Simulation of the devices' dynamic performance by applying their frequency responses to a high-fidelity recording of arterial pressure demonstrated that the devices have sufficient bandwidth to accurately record arterial waveform dynamics. Experiments were also performed to determine how routine laboratory use and maintenance of the catheter affects the frequency response of the telemeters. Provided no air bubbles were introduced, these showed that the telemeters' frequency responses were robust to the maintenance procedures of tip removal and gel application. 6. The frequency response measurements, combined with simulation results, demonstrate that the systems tested have adequate dynamic performance to record arterial pressure.

Novel technology for the provision of power to implantable physiological devices.

We report the development of a novel technology that enables the wireless transmission of sufficient amounts of power to implantable physiological devices. The system involves a primary unit generating the magnetic field and a secondary pickup unit deriving power from the magnetic field and a power conditioner. The inductively coupled system was able to supply a minimum of 20 mW at all locations and pickup orientations across a rat cage, although much higher power of up to 10 W could be achieved. We hypothesized that it would be possible to use this technology to record a high-fidelity ECG signal in a conscious rat. A device was constructed in which power was utilized to recharge a battery contained within a telemetry device recording ECG signal sampled at 2,000 Hz in conscious rats (200-350 g) living in their home cage. Attributes of the ECG signal (QT, QRS, and PR interval) could be obtained with a high degree of accuracy (<1 ms). ECG and heart rate changes in response to treatment with the beta blocker propranolol and the proarrhythmic alkaloid aconitine were measured. Transmitters were implanted for up to 4 mo, and the characteristic circadian variation in heart rate was recorded. Such technology allows potentially lifetime monitoring without the need for implant refurbishment. The ability to provide suitable power levels to implanted devices without concern to the orientation of the device and without causing heating provides the basis for the development of new devices to record or influence physiological signals in animals or humans over significantly longer time periods than can currently be accommodated.

Baroreflex mechanisms regulating mean level of SNA differ from those regulating the timing and entrainment of the sympathetic discharges in rabbits.

The arterial baroreflex pathway provides the fundamental basis for the short-term control of blood pressure via the rapid regulation of the mean level of sympathetic nerve activity (SNA) in response to changes in blood pressure. A central tenet in the generation and regulation of bursts of SNA is that input from the arterial baroreceptors also regulates the timing of the bursts of sympathetic activity. With the use of an implantable telemetry-based amplifier, renal SNA was recorded in intact and arterial baroreceptor-denervated (SAD) conscious rabbits. Data were collected continuously while animals were in their home cage. Mean levels of SNA were not different between SAD and baroreceptor-intact animals. Whereas SNA was unresponsive to changes in blood pressure in SAD rabbits, the timing of the bursts of SNA relative to the arterial pulse wave was maintained (time between the diastolic pressure and the next maximum SNA voltage averaged 107+/-12 ms SAD vs. 105+/-7 ms intact). Transfer function analysis between blood pressure and SNA indicates the average gain at the heart rate frequency was not altered by SAD, indicating strong coupling between the cardiac cycle and SNA bursts in SAD animals. Further experiments in anesthetized rabbits showed that this entrainment is lost immediately after performing baroreceptor denervation surgery and remained absent while the animal was under anesthesia but returned within 20 min of turning off the anesthesia. We propose that this finding indicates the regulation of the mean level of SNA requires the majority of input from baroreceptors to be functional; however, the regulation of the timing of the bursts in the conscious animal requires only minimal input, such as a sensitive trigger mechanism. This observation has important implications for understanding the origin and regulation of SNA.

What sets the long-term level of renal sympathetic nerve activity: a role for angiotensin II and baroreflexes?

Increasing evidence suggests elevated sympathetic outflow may be important in the genesis of hypertension. It is thought that peripheral angiotensin II, in addition to its pressor actions, may act centrally to increase sympathetic nerve activity (SNA). Without direct long-term recordings of SNA, testing the involvement of neural mechanisms in angiotensin II-induced increases in arterial pressure is difficult. Using a novel telemetry-based implantable amplifier, we made continuous recordings of renal SNA (RSNA) before, during, and after 1 week of angiotensin II-based hypertension in rabbits living in their home cages. Angiotensin II infusion (50 ng x kg(-1) x min(-1)) caused a sustained increase in arterial pressure (18+/-3 mm Hg). There was a sustained decrease in RSNA from 18+/-2 normalized units (n.u.) before angiotensin II to 8+/-2 n.u. on day 2 and 9+/-2 n.u. on day 7 of the angiotensin II infusion (P<0.01) before recovering to 17+/-2 n.u. after ceasing angiotensin II. Analysis of the baroreflex response showed that although angiotensin II-induced hypertension led to resetting of the relationship between mean arterial pressure (MAP) and heart rate, there was no evidence of resetting of the MAP-RSNA relationship. We propose that the lack of resetting of the MAP-RSNA curve, with the resting point lying near the lower plateau, suggests the sustained decrease in RSNA during angiotensin II is baroreflex mediated. These results suggest that baroreflex control of RSNA and thus renal function is likely to play a significant role in the control of arterial pressure not only in the short term but also in the long term.