We determined the status of kidney tissue oxygenation during the subacute phase of renal ischemia reperfusion injury in 10‐12 week old male Sprague‐Dawley rats. Inner medullary oxygen tension (PO2) was determined using a carbon paste electrode attached to a telemetry transmitter, for 24 hours before and for 5 days after 60 min of bilateral renal ischemia (n=4) or sham (n=4) surgery. In a second protocol, renal tissue PO2 was measured by Clark electrode under thiobutabarbital anesthesia, either 1 or 5 days after recovery from renal ischemia (n = 6 and 3 respectively) or sham surgery (n = 5 and 3 respectively). Inner medullary tissue PO2 measured by telemetry was increased by 45 ± 15% 24 h after reperfusion, but then progressively fell over the next 5 days. Tissue PO2 measured by Clark electrode was well maintained 24 h after ischemia. However, outer medullary PO2 was 69% less 5 days after ischemia than after sham surgery. Our observations suggest that widespread renal hypoxia may not be obligatory in the subacute phase of renal ischemia‐reperfusion injury. However, medullary hypoxia may evolve over a period of days following reperfusion.Grant Funding Source: Supported by the National Health and Medical Research Council of Australia

Multiple forms of acute and chronic kidney disease are associated with renal tissue hypoxia. This has led to the proposition that renal hypoxia is not just a consequence of kidney disease, but rather a primary pathogenic event. Using telemetric technology to chronically measure the partial pressure of oxygen (PO2), we recorded cortical PO2 during the early stages of development of chronic kidney disease (CKD) in conscious rats. Male Wistar rats underwent 5/6 subtotal nephrectomy (n = 4) or sham (n = 4) surgery. After an initial increase, cortical PO2 values decreased in the first 2 weeks after induction of CKD and thereafter remained stable for the subsequent 6 weeks with an average reduction of 42 ± 12% compared to baseline. Sham operation had little effect on cortical PO2. The decrease in tissue PO2 in the remnant kidney occurred before proteinuria and uremia suggesting that hypoxia precedes the symptoms of CKD and therefore could be a major driver of the subsequent pathology. This is consistent with the hypothesis that kidney hypoxia is central in the pathogenesis of CKD.Grant Funding Source: EU, FP7, Marie Curie Actions, International Outgoing Fellowship

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. Together this organization produces sympathetic responses tailored to match stimuli. The long-term control of sympathetic nerve activity (SNA) is an area of considerable interest and involves a variety of mediators acting in a quite distinct fashion. These mediators include arterial baroreflexes, angiotensin II, blood volume and osmolarity, and a host of humoral factors. A key feature of many cardiovascular diseases is increased SNA. However, rather than there being a generalized increase in SNA, it is organ specific, in particular to the heart and kidneys. These increases in regional SNA are associated with increased mortality. Understanding the regulation of organ-specific SNA is likely to offer new targets for drug therapy. There is a need for the research community to develop better animal models and technologies that reflect the disease progression seen in humans. A particular focus is required on models in which SNA is chronically elevated.

The pending expiry (May 2008) of a Data Sciences (DSI) patent in the area of blood pressure telemetry permits the development of alternative technologies. A key aspect in providing new telemetry systems is a comparison to existing technology. Important aspects include stability of the calibration over time and the ability to capture the pulsitile blood pressure waveform. In a group of 6 rats and 5 rabbits DSI blood pressure transmitters (C40 or D70 models) were implanted in conjunction with Telemetry Research (TR) transmitters. Both systems incorporate a fluid filled catheter of similar dimensions with a biocompatible gel in the tip. The blood pressure waveform was collected via telemetry for up to 2 months after implantation. The signal was sampled at 500 Hz and digitally transmitted to a receiver up to 5 m away The battery of TR transmitter was recharged within the rat using inductive power transfer technology. The pulsitile waveform associated with each heart beat was reflected similarly in all cases although the frequency response of DSI telemeters was limited to ~40 Hz (−3 dB rolloff point). The calibrated offset level between the two transmitters was not more than 5 mmHg at all times over a 2 month period. We conclude that the Telemetry Research blood pressure transmitters offer comparable performance to existing technology but with extra design advantages (rechargeable, co‐housing of animals, greater range).

We report on the development of a combined sympathetic nerve activity and blood pressure telemeter for long term implantation in freely moving small animals. The devices simultaneously records and transmits blood pressure, temperature and sympathetic nerve data on the 2.4 GHz ISM band with a range of 5 m. Blood pressure is measured with a 400 Hz bandwidth, fluid filled catheter at a resolution of 0.1 mmHg. Sympathetic nerve activity is measured differentially using stainless steel electrodes attached to the renal nerve. The telemeter measures 29x37x12min (a volume of approximately 9.5 cm(3)) and weighs 17g, making it suitable for use in rats with a weight greater than 170 g. Battery life is 12 h when used continuously, however the device's lifespan is effectively indefinite due to the use of in vivo inductively coupled battery charging. Example data recorded in a conscious unconstrained rat is provided which verifies the telemeters operation.

The control of blood pressure is a complex mixture of neural, hormonal and intrinsic interactions at the level of the heart, kidney and blood vessels. While experimental approaches to understanding these interactions are useful, it remains difficult to conduct experiments to quantify these interactions as the number of parameters increases. Thus, modelling of such physiological systems can offer considerable assistance. Typical mathematical models which describe the ability of the blood vessels to change their diameter (vasoconstriction) assume linearity of operation. However, due to the interaction of multiple vasocontrictive and vasodilative effectors, there is a significant nonlinear response to the influence of neural factors, particularly at higher levels of nerve activity (often seen in subjects with high blood pressure) which leads to low blood flow rates. This paper proposes a number of nonlinear mathematical models for the relationship between neural influences (sympathetic nerve activity (SNA)) and renal blood flow, using a feedback path to model the predominantly nonlinear effect of local vasoactive modulators such as nitric oxide, which oppose the action of SNA. The model structures are motivated by basic physiological principles, while the model parameters are determined using numerical optimisation techniques using open-loop data collected from rabbits. The models were verified by demonstrating correlation between experimental results and model outputs.

This paper presents a novel method of inductively powering an implantable telemetry device over a large area. The system is based around an array of individually tuned series resonant circuits distributed across a charging pad. By varying the frequency of the driving voltage, the location of the charging field is changed. Presented are a method of controlling the resonant frequency and techniques for determining the geometry of the charging pad. Results from a nine coil system operating between 97 kHz and 209 kHz are given which can deliver 100 mW to an implanted telemeter at a height of 5 cm above the charging pad.

Low frequency oscillations in blood pressure (BP) can occur due to a feedback pathway between the sensing of BP and the central nervous system (CNS),oftentermedthebarore∞ex,afiectingbothcardiacoutput(heart-rateand stroke volume) and peripheral resistance. In this paper, an integrated model of both these subsystems is assembled and an analysis technique developed, which showstheconditionsunderwhichalimitcycleoscillationcanoccur.Inparticular, the role of mean levels of cardiac output and peripheral resistance, previously thought to be relatively unimportant, in establishing and maintaining sustained oscillations, is highlighted. The ultimate aim of this analysis is to assist in the development of diagnostic tests based on measurement of low-frequency blood pressureoscillations. Copyright c ∞2005 IFAC