The Safety of Micro-Implants for the Brain.

Technological advancements in electronics and micromachining now allow the development of discrete wireless brain implantable micro-devices. Applications of such devices include stimulation or sensing and could enable direct placement near regions of interest within the brain without the need for electrode leads or separate battery compartments that are at increased risk of breakage and infection. Clinical use of leadless brain implants is accompanied by novel risks, such as migration of the implant.

Selective optogenetic stimulation of efferent fibers in the vagus nerve of a large mammal.

Background: Electrical stimulation applied to individual organs, peripheral nerves, or specific brain regions has been used to treat a range of medical conditions. In cardiovascular disease, autonomic dysfunction contributes to the disease progression and electrical stimulation of the vagus nerve has been pursued as a treatment for the purpose of restoring the autonomic balance. However, this approach lacks selectivity in activating function- and organ-specific vagal fibers and, despite promising results of many preclinical studies, has so far failed to translate into a clinical treatment of cardiovascular disease.

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.

Intracranial pressure influences the level of sympathetic tone.

Sympathetic overdrive is associated with many diseases, but its origin remains an enigma. An emerging hypothesis in the development of cardiovascular disease is that the brain puts the utmost priority on maintaining its own blood supply; even if this comes at the "cost" of high blood pressure to the rest of the body. A critical step in making a causative link between reduced brain blood flow and cardiovascular disease is how changes in cerebral perfusion affect the sympathetic nervous system.

Exogenous and endogenous angiotensin-II decrease renal cortical oxygen tension in conscious rats by limiting renal blood flow.

Key Points: Our understanding of the mechanisms underlying the role of hypoxia in the initiation and progression of renal disease remains rudimentary. We have developed a method that allows wireless measurement of renal tissue oxygen tension in unrestrained rats. This method provides stable and continuous measurements of cortical tissue oxygen tension (PO2) for more than 2 weeks and can reproducibly detect acute changes in cortical oxygenation.

Prolonged and Continuous Measurement of Kidney Oxygenation in Conscious Rats.

A relative deficiency in kidney oxygenation, i.e., renal hypoxia, may contribute to the initiation and progression of acute and chronic kidney disease.

Recording of intracranial pressure in conscious rats via telemetry.

Although cerebral perfusion pressure (CPP) is known to be fundamental in the control of normal brain function, there have been no previous long-term measurements in animal models. The aim of this study was to explore the stability and viability of long-term recordings of intracranial pressure (ICP) in freely moving rats via a telemetry device. We also developed a repeatable surgical approach with a solid-state pressure sensor at the tip of the catheter placed under the dura and in combination with arterial pressure (AP) measurement to enable the calculation of CPP.

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.

Arterial baroreceptor reflex control of renal sympathetic nerve activity following chronic myocardial infarction in male, female, and ovariectomized female rats.

There is controversy regarding whether the arterial baroreflex control of renal sympathetic nerve activity (SNA) in heart failure is altered. We investigated the impact of sex and ovarian hormones on changes in the arterial baroreflex control of renal SNA following a chronic myocardial infarction (MI). Renal SNA and arterial pressure were recorded in chloralose-urethane anesthetized male, female, and ovariectomized female (OVX) Wistar rats 6-7 wk postsham or MI surgery.

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.

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.

Telemetry-based oxygen sensor for continuous monitoring of kidney oxygenation in conscious rats.

The precise roles of hypoxia in the initiation and progression of kidney disease remain unresolved. A major technical limitation has been the absence of methods allowing long-term measurement of kidney tissue oxygen tension (Po₂) in unrestrained animals. We developed a telemetric method for the measurement of kidney tissue Po₂ in unrestrained rats, using carbon paste electrodes (CPEs).

Effects of sex and ovarian hormones on the initial renal sympathetic nerve activity response to myocardial infarction.

The physiological mechanisms contributing to sex differences following myocardial infarction (MI) are poorly understood. Given the strong relationship between sympathetic nerve activity (SNA) and outcome, we hypothesized there may be a sex difference in SNA responses to MI. In anaesthetized, open-chest male, female and ovariectomized (OVX) female Wistar rats, mean arterial pressure, heart rate and renal SNA were recorded in response to ligation of the left coronary artery.

Renal sympathetic nerve activity during asphyxia in fetal sheep.

The sympathetic nervous system (SNS) is an important mediator of fetal adaptation to life-threatening in utero challenges, such as asphyxia. Although the SNS is active well before term, SNS responses mature significantly over the last third of gestation, and its functional contribution to adaptation to asphyxia over this critical period of life remains unclear. Therefore, we examined the hypotheses that increased renal sympathetic nerve activity (RSNA) is the primary mediator of decreased renal vascular conductance (RVC) during complete umbilical cord occlusion in preterm fetal sheep (101 ± 1 days; term 147 days) and that near-term fetuses (119 ± 0 days) would have a more rapid initial vasomotor response, with a greater increase in RSNA.

Cardiovascular and autonomic responses to sexual activity in the rabbit.

1. Sexual intercourse is associated with an increased risk of death from arrhythmia development, myocardial infarction or stroke. It is unclear whether this increased risk is due to physical exertion alone or whether it is an inherent aspect of sexual activity itself.

High dietary salt and angiotensin II chronically increase renal sympathetic nerve activity: a direct telemetric study.

Overactivity of the sympathetic nervous system has long been implicated in the hypertensive response to elevated angiotensin II (Ang II) levels. Although recent studies suggest that high dietary salt may alter cardiovascular responses to Ang II, direct evidence demonstrating chronic activation of sympathetic nerve activity is lacking. The objective of this study was to determine whether a low dose of Ang II, on a background of high salt intake, would result in a chronic increase in renal sympathetic nerve activity (RSNA).

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.

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.

Baroreflex control of renal sympathetic nerve activity and heart rate in near-term fetal sheep.

Late preterm infants, born between 34 and 36 weeks gestation, have significantly higher morbidity than neonates born at full term, which may be partly related to reduced sensitivity of the arterial baroreflex. The present study assessed baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) in near-term fetal sheep at 123 ± 1 days gestation. At this age, although fetuses are not fully mature in some respects (term is 147 days), sleep-state cycling is established [between high-voltage, low-frequency (HV) and low-voltage, high-frequency (LV) sleep], and neural myelination is similar to the term human infant.

Maturation-related changes in the pattern of renal sympathetic nerve activity from fetal life to adulthood.

Sympathetic nerve activity (SNA) has two main properties, the presence of co-ordinated bursts of activity, indicative of many nerve fibres firing at a similar time, and entrainment of the bursts to the cardiac cycle, due to inhibitory input from baroreceptors to a network of cell groups within the CNS. Although this patterning is used as a 'gold standard' for the identification of successful nerve recordings, the maturation of these basic features of SNA from fetal life to adulthood has not been investigated. Using a telemetry-based nerve amplifier, renal SNA (RSNA) was recorded in preterm (99 ± 1 days gestation; term 147 days) and near-term fetal sheep (119 ± 0 days gestation), without anaesthesia or paralysis, and contrasted with RSNA recorded in adult sheep.

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.

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.

Sympathetic nervous system overactivity and its role in the development of cardiovascular disease.

This review examines how the sympathetic nervous system plays a major role in the regulation of cardiovascular function over multiple time scales. This is achieved through differential regulation of sympathetic outflow to a variety of organs. This differential control is a product of the topographical organization of the central nervous system and a myriad of afferent inputs.

Quantifying sympathetic nerve activity: problems, pitfalls and the need for standardization.

Since the first recording of sympathetic nerve activity (SNA) early last century, numerous methods for presentation of the resulting data have developed. In this paper, we discuss the common ways of describing SNA and their application to chronic recordings. Suggestions on assessing the quality of SNA are made, including the use of arterial pressure wave-triggered averages and nasopharyngeal stimuli.

A high-salt diet does not influence renal sympathetic nerve activity: a direct telemetric investigation.

The importance of dietary salt in the development of hypertension has long been a source of controversy. Recent studies suggest a combination of high-salt and ANG II infusion may increase sympathetic drive; however, the effect of a change in dietary salt alone is unclear. Using telemetry, we recorded renal sympathetic nerve activity (RSNA), arterial pressure (MAP), and heart rate (HR) in seven New Zealand white rabbits before and during a 6-day period of increased salt intake (normal NaCl 0.