Simon C. Malpas

A Frequency Control Method for Regulating Wireless Power to Implantable Devices

This paper presents a method to regulate the power transferred over a wireless link by adjusting the resonant operating frequency of the primary converter. A significant advantage of this method is that effective power regulation is maintained under variations in load, coupling and circuit parameters. This is particularly important when the wireless supply is used to power implanted medical devices where substantial coupling variations between internal and external systems is expected. The operating frequency is changed dynamically by altering the effective tuning capacitance through soft switched phase control. A thorough analysis of the proposed system has been undertaken, and experimental results verify its functionality.

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

Abstract— 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 · kg−1 · 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.

The rhythmicity of sympathetic nerve activity

This review focuses on that most engaging feature of the sympathetic nervous system, its rhythmicity. In particular examining the nature of sympathetic nerve activity (SNA), its characteristics, the frequencies of these rhythms and possible mechanisms responsible for their generation. Sympathetic activity can be thought of as a complex output of the central nervous system providing subtle control over end organ function. This control is exerted in a number of frequency bands including rhythms related to the cardiac and respiratory cycles, 10 Hz, and between 0.2 and 0.4 Hz. The generation and control over the occurrence of each of these rhythms is likely to be quite separate. Although afferent feedback from sources such as baroreceptors can explain some of the rhythmical properties in each case there is good evidence for inherent generation of aspects of these rhythms. A variety of brainstem cell groups are thought to be involved in their generation with the rostral ventrolateral medulla, although unlikely to be solely responsible for tone generation, an important regulator of overall activity. SNA also varies in the number of nerves recruited to fire in each synchronized discharge. Little is known about this control other than it appears to be quite separate from the control over the timing of discharges. Spinal cord mechanisms are possibly involved. SNA frequencies above 0.7 Hz do not appear to directly induce oscillations in innervated vasculature, however, are likely to contribute to setting the level of vasconstrictive tone. Slower frequencies appear to directly cause oscillations in blood flow.

SYMPATHETIC BURST ACTIVITY: CHARACTERISTICS AND SIGNIFICANCE

1. The activity recorded from mammalian sympathetic nerves comes in bursts, which result from large numbers of fibres firing synchronously.

Wireless Power Supply for Implantable Biomedical Device Based on Primary Input Voltage Regulation

This paper presents a wireless power supply system for implantable biomedical devices. Magnitude of the input voltage supplied to the primary power converter is dynamically regulated according to the power demand of the device. The major advantage of such a system is that its average power loss is minimized. Unlike methods implemented at implantable secondary (pick-up) side, the magnitude regulation is undertaken at the external primary side. Thus the heating effect and physical size of the implantable secondary can be reduced. The system utilizes parallel tuning circuit to boost the voltage induced in the secondary pick-up, and does not require a tight coupling between the primary and secondary coils. As a result, the system has great tolerance to the variation in the air gap distance between the coils. The characteristics of the magnitude regulated power flow have been thoroughly analyzed, and both simulations and laboratory experiments have verified the proposed system.

Baroreceptor Denervation Prevents Sympathoinhibition During Angiotensin II–Induced Hypertension

Arterial baroreflexes are well established to provide the basis for short-term control of arterial pressure; however, their role in long-term pressure control is more controversial. We proposed that if the sustained decrease in renal sympathetic nerve activity (RSNA) we observed previously in response to angiotensin II–induced hypertension is baroreflex mediated, then the decrease in RSNA in response to angiotensin II would not occur in sinoaortic-denervated (SAD) animals. Arterial pressure and RSNA were recorded continuously via telemetry in sham and SAD rabbits living in their home cages before, during, and after a 7-day infusion of angiotensin II (50 ng · kg−1 · min−1). The arterial pressure responses in the 2 groups of rabbits were not significantly different (82±3 mm Hg sham versus 83±3 mm Hg SAD before angiotensin II infusion, and 101±6 mm Hg sham versus 100±4 mm Hg SAD day 6 of angiotensin II). In sham rabbits, there was a significant sustained decrease in RSNA (53±7% of baseline on day 2 and 65±7% on day 6 of the angiotensin II). On ceasing the angiotensin II, all variables recovered to baseline. In contrast, RSNA did not change in SAD rabbits with the angiotensin II infusion (RSNA was 98±8% of baseline on day 2 and 98±8% on day 6 of the angiotensin II infusion). These results support our hypothesis that the reduction in RSNA in response to a pressor dose of angiotensin II is dependent on an intact arterial baroreflex pathway.

Contribution of renal nerves to renal blood flow variability during hemorrhage

We have examined the role of the renal sympathetic nerves in the renal blood flow (RBF) response to hemorrhage in seven conscious rabbits. Hemorrhage was produced by blood withdrawal at 1.35 ml.min(-1).kg-1 for 20 min while RBF and renal sympathetic nerve activity (RSNA) were simultaneously measured. Hemorrhage was associated with a gradual increase in RSNA and decrease in RBF from the 4th min. In seven denervated animals, the resting RBF before hemorrhage was significantly greater (48 +/- 1 vs. 31 +/- 1 ml/min intact), and the decrease in RBF did not occur until arterial pressure also began to fall (8th min); however, the overall percentage change in RBF by 20 min of blood withdrawal was similar. Spectral analysis was used to identify the nature of oscillations in each variable. Before hemorrhage, a rhythm at approximately 0.3 Hz was observed in RSNA, although not in RBF, whose spectrogram was composed mostly of lower-frequency (< 0.25 Hz) components. The denervated group of rabbits had similar frequency spectrums for RBF before hemorrhage. RSNA played a role in dampening the effect of oscillations in arterial pressure on RBF as the transfer gain between mean arterial pressure (MAP) and RBF for frequencies > 0.25 Hz was significantly less in intact than denervated rabbits (0.83 +/- 0.12 vs. 1.19 +/- 0.10 ml.min(-1).mmHg-1). Furthermore, the coherence between MAP and RBF was also significantly higher in denervated rabbits, suggesting tighter coupling between the two variables in the absence of RSNA. Before the onset of significant decreases in arterial pressure (up to 10 min), there was an increase in the strength of oscillations centered around 0.3 Hz in RSNA. These wer accompanied by increases in the spectral power of RBF at the same frequency. Arterial pressure fell in both groups of animals, the dominant rhythm to emerge in RBF was centered between 0.15 and 0.20 Hz and was present in intact and denervated rabbits. It is speculated that this myogenic in origin. We conclude that RSNA can induce oscillations in RBF at 0.3 Hz, plays a significant role in altering the effect of oscillations in arterial pressure on RBF, and mediates a proportion of renal vasoconstriction during hemorrhage in conscious rabbits.We have examined the role of the renal sympathetic nerves in the renal blood flow (RBF) response to hemorrhage in seven conscious rabbits. Hemorrhage was produced by blood withdrawal at 1.35 ml ⋅ min-1 ⋅ kg-1for 20 min while RBF and renal sympathetic nerve activity (RSNA) were simultaneously measured. Hemorrhage was associated with a gradual increase in RSNA and decrease in RBF from the 4th min. In seven denervated animals, the resting RBF before hemorrhage was significantly greater (48 ± 1 vs. 31 ± 1 ml/min intact), and the decrease in RBF did not occur until arterial pressure also began to fall (8th min); however, the overall percentage change in RBF by 20 min of blood withdrawal was similar. Spectral analysis was used to identify the nature of the oscillations in each variable. Before hemorrhage, a rhythm at ∼0.3 Hz was observed in RSNA, although not in RBF, whose spectrogram was composed mostly of lower-frequency (<0.25 Hz) components. The denervated group of rabbits had similar frequency spectrums for RBF before hemorrhage. RSNA played a role in dampening the effect of oscillations in arterial pressure on RBF as the transfer gain between mean arterial pressure (MAP) and RBF for frequencies >0.25 Hz was significantly less in intact than denervated rabbits (0.83 ± 0.12 vs. 1.19 ± 0.10 ml ⋅ min-1 ⋅ mmHg-1). Furthermore, the coherence between MAP and RBF was also significantly higher in denervated rabbits, suggesting tighter coupling between the two variables in the absence of RSNA. Before the onset of significant decreases in arterial pressure (up to 10 min), there was an increase in the strength of oscillations centered around 0.3 Hz in RSNA. These were accompanied by increases in the spectral power of RBF at the same frequency. As arterial pressure fell in both groups of animals, the dominant rhythm to emerge in RBF was centered between 0.15 and 0.20 Hz and was present in intact and denervated rabbits. It is speculated that this is myogenic in origin. We conclude that RSNA can induce oscillations in RBF at 0.3 Hz, plays a significant role in altering the effect of oscillations in arterial pressure on RBF, and mediates a proportion of renal vasoconstriction during hemorrhage in conscious rabbits.

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). Arterial pressure and RSNA were recorded via telemetry. Two groups of rabbits were studied: 1 group drank a 0.9% NaCl solution and received Ang II (20 ng/kg per minute for 21 days, Salt+Ang), and the other drank tap water throughout and was not infused with Ang II (Control). In the Salt+Ang group, mean arterial pressure increased over the first week and remain elevated by 18.5±4.1 mm Hg at day 21. RSNA was not significantly different between groups on day 7 but was significantly elevated in the Salt+Ang group on day 21 (13.5±3.2% compared with 6.8±0.8% in the Control group; P<0.05). Baroreflex control of RSNA showed a rightward shift on day 21, but not day 7, and baroreflex responses indicated that RSNA could not be completely suppressed when arterial pressure was increased. No changes were observed in either mean arterial pressure or RSNA variables in the Control group. Our results support the hypothesis that elevated Ang II levels, in conjunction with a high salt diet, have the ability to chronically increase RSNA and, thus, potentially contribute to the maintenance of hypertension.

Do different levels and patterns of sympathetic activation all provoke renal vasoconstriction

Renal sympathetic nerve activity (RSNA) is postulated to influence renal function in selective ways with changes in renal hemodynamics only occurring during high stimulus intensities. The aim of this study was to determine the renal blood flow (RBF) response to a number of stimuli designed to increase RSNA by a modest amount and assess the possibility that different afferent stimuli produce differential levels of vasoconstriction by differentially altering the pattern of RSNA. Experiments were performed in eight conscious rabbits subjected to 20 min periods of three stimuli noise stress, air jet stress or hypoxia (10% O2). RSNA was significantly increased 12 +/- 4, 31 +/- 8 and 14 +/- 5% (means of 20 min periods +/- SEM) and these effects were mirrored in the significant changes in RBF over the period of each stimuli with mean reductions of 8 +/- 1, 10 +/- 3 and 8 +/- 4% during noise, air jet stress and hypoxia respectively. Changes in plasma renin activity did not occur without changes in RBF. With regard to the pattern of RSNA discharges, hypoxia selectively increased the amplitude (number of recruited nerves) while noise and air jet stress increased both the amplitude and frequency of discharges. The role of the renal nerves in these responses and in providing a tonic level of vasoconstriction within the kidney, was demonstrated in experiments on a group of eight renal denervated animals. The renal denervated rabbits had greater resting RBF than the intact rabbits (54 +/- 1 denervated vs. 38 +/- 1 ml min(-1) intact), and RBF was not altered by any of the afferent stimuli. We conclude that small changes in RSNA, irrespective of the stimulus, modulate renal blood flow.

The amplitude and periodicity of synchronized renal sympathetic nerve discharges in anesthetized cats: differential effect of baroreceptor activity

We applied a computerized peak detection algorithm to recordings of synchronized sympathetic nerve discharges from anesthetized cats to retrieve information about the characteristics of renal nerve activity (RNA) during changes in baroreceptor activity. The algorithm scanned the series of RNA voltages for significant increases followed by significant decreases in a small cluster of voltage values. Once each synchronized RNA peak had been detected, its corresponding amplitude, width and peak-to-peak interval were calculated. The peak-to-peak interval periodicity showed two modes of synchronized discharge, one between 200-500 ms accounting for 47% of intervals, and a higher 20-180 ms frequency (49% of intervals). Baroreceptor stimulation decreased the occurrence of the high frequencies while increasing the probability of the lower frequency components. The overall occurrence of synchronized peaks per second fell linearly to zero with increases in blood pressure. The peak amplitude of RNA was unimodally distributed and was not affected by baroreceptor stimulation until an increase in mean arterial pressure reached a threshold (mean 142 +/- 5 mmHg) whereupon it fell quickly to zero. Sino-aortic vagal denervation did not affect the distribution of peak height. The width of synchronized discharges was also unimodal, mean 82 +/- 1 ms, and was almost unchanged during baroreflex stimulation acting in parallel with changes in the peak amplitude and decreasing at high blood pressures. Sino-aortic vagal denervation did not affect the synchronized width. There was no relationship between the periodicity and amplitude or width of synchronized discharges under all conditions. The results indicate that the periodicity and amplitude of renal synchronized discharges appear to be independent of each other and are differentially affected by baroreceptor input.