The sustained reduction in blood pressure after a single bout of aerobic or resistance exercise (RE) has gained significant clinical relevance in hypertensive individuals. This phenomenon is known as post-exercise hypotension (PEH). However, the neural mechanisms that lead to HPE still need to be better understood, particularly arising from the ER. In this sense, the present study sought to review the neural mechanisms involved in HPE and evaluate the hemodynamic and autonomic control changes induced by ER in hypertensive rats induced by Nω-nitro-Larginine methyl ester (L-NAME). The thesis consists of two chapters, which are systematic review and an original article. Initially was elaborated a systematic review "A systematic review of neural mechanisms involved on post-exercise hypotension in hypertensive animals", with search for articles in LILACS, EMBASE and PUBMED database, which describes an overview of the neural mechanisms involved in HPE in studies of hypertensive animals. These studies demonstrated the presence of cardiovascular afferents, afferent skeletal muscle stimulation during exercise and bulbar or suprabulbar modulations are fundamental to the expression of HPE. After completion of the experimental protocols the article: "Arterial Baroreflex participates in the post-resistance exercise hypotension in L-NAME-induced hypertensive rats", was presented. This paper demonstrated that the increased baroreflex arterial sensitibity REinduced plays a crucial role in PEH followed by bradycardia, probably through cardiac and vascular sympathetic inhibition. Together, these findings show that the involvement of neural mechanisms are important for the manifestation of PEH induced by both aerobic and resistance exercise in hypertensive rats. / A redução sustentada da pressão arterial após uma única sessão de exercício aeróbico ou resistido (ER) tem ganhado significativa relevância clínica em indivíduos hipertensos. Esse fenômeno é conhecido como hipotensão pós-exercício (HPE). No entanto, os mecanismos neurais que levam a HPE ainda necessitam serem melhor compreendidos, especialmente decorrentes do ER. Neste sentido, o presente trabalho buscou revisar os mecanismos neurais envolvidos na HPE e avaliar as alterações hemodinâmicas e controle autonômico provocadas pelo ER em ratos hipertensos induzidos por Nω-Nitro-L-arginina metil éster (L-NAME). A tese é composta por dois capítulos, constituídos de uma revisão sistemática e um artigo original. Inicialmente foi elaborada a revisão sistemática A systematic review of neural mechanisms involved on post-exercise hypotension in hypertensive animals , com busca dos artigos nos bancos de dados LILACS, PUBMED e EMBASE, a qual descreve uma visão geral dos mecanismos neurais envolvidos na HPE em estudos realizados com animais hipertensos. Esses estudos demonstraram que a presença de aferência cardiovascular, estímulo da aferência muscular esquelética durante o exercício e modulações suprabulbares são fundamentais para a expressão da HPE. Após a realização dos protocolos experimentais foi elaborado o artigo Arterial Baroreflex participates in the post-resistance exercise hypotension in L-NAMEinduced hypertensive rats . Este artigo demonstrou que o aumento da sensibilidade do barorreflexo arterial induzido pelo ER desempenha um papel crucial na HPE seguida de bradicardia, provavelmente através da inibição simpática cardíaca e vascular. Juntos, esses achados permitem concluir que a participação de mecanismos neurais são importantes para a manifestação da HPE induzido por ambos os tipos de exercício aeróbico e resistido em ratos hipertensos.

INTRODUÇÃO: Informações da literatura associam a obesidade a maior atividade simpática. A gastroplastia com derivação gastrojejunal em Y de Roux, que leva a redução rápida e intensa do peso, pode influenciar o padrão autonômico cardiovascular. O objetivo deste estudo é avaliar os efeitos dessa cirurgia sobre a modulação autonômica do coração, tolerância ortostática e excreção urinária de noradrenalina. METODOS: Trata-se de um estudo observacional longitudinal, realizado na cidade de Maringá - PR, com 71 pacientes, incluídos no período de julho de 2004 a dezembro de 2005, avaliados antes e seis meses após a cirurgia. Foram estudados 42 mulheres e 29 homens, com idade variando de 18 a 66 anos (mediana de 36 anos) e índice de massa corpórea (IMC) variando de 37,1 a 56,2 kg/m2 (mediana de 41,9 kg/m2). Do total, 28 eram hipertensos. Não foram incluídos pacientes com diagnóstico de diabetes melito. Análise da variabilidade da freqüência cardíaca no domínio do tempo através de gravações de Holter 24 horas, teste de inclinação ortostática e dosagem de noradrenalina em urina de 24 horas foram realizadas nas duas fases do estudo. Também foram avaliados glicemia e insulina de jejum, perfil lipídico, proteína C-reativa de alta sensibilidade, fibrinogênio e qualidade de vida através do questionário SF-36. RESULTADOS: A redução média do peso, seis meses após a cirurgia, foi de 25,46% e da circunferência abdominal, de 20,4%. A freqüência sinusal se reduziu significativamente, expressa pelo aumento do intervalo NN médio (p<0,001). Os índices da variabilidade da freqüência cardíaca SDNN, SDANN, SDNN index, pNN50 e rMSSD apresentaram aumento significativo (p<0,001, p<0,001, p=0,002, p=0,001 e p=0,002, respectivamente). Os homens apresentaram maior elevação do SDNN e SDANN do que as mulheres (p=0,006 e p=0,007, respectivamente). A idade foi fator significativo para a evolução do SDNN index (p=0,015) e rMSSD (p=0,002), reduzindo-se o aumento com o avanço da idade. A redução da circunferência abdominal apresentou melhor correlação com o aumento da variabilidade da freqüência cardíaca que as reduções do peso e IMC. Nenhum paciente apresentou sintoma novo de intolerância ortostática após a cirurgia. A resposta vasovagal ao teste de inclinação não apresentou diferença significativa entre as duas fases do estudo. A resposta disautonômica foi encontrada em apenas dois casos, após a cirurgia, fato que não permitiu a avaliação deste tipo de resposta. Não houve nenhum caso de hipotensão ortostática sintomática. Houve redução do número de casos de hipotensão ortostática assintomática, com razão de chance para a ocorrência após a cirurgia, em relação ao pré-operatório, de 0,10 (p=0,030). Não houve diferença nos níveis de noradrenalina urinária entre o pré e o pós-operatório. Houve redução da glicemia e insulina de jejum, melhora do perfil lipídico e redução da proteína C-reativa de alta sensibilidade, sem modificação do fibrinogênio. A qualidade de vida apresentou melhora. CONCLUSÃO: A gastroplastia com derivação gastrojejunal modificou o padrão autonômico, aumentando a ação parassimpática sobre o nó sinusal, evidenciada pelo aumento da variabilidade da freqüência cardíaca. A mudança ocorreu sem piora clínica da tolerância ortostática e sem aumento da suscetibilidade à síncope vasovagal. / INTRODUCTION: Findings from literature associate obesity with increased sympathetic activity. Roux-en-Y gastric bypass, which promotes large and rapid weigh loss, can influence the autonomic cardiovascular activity. The aim of the present study was to evaluate the influence of surgery on the heart autonomic modulation, orthostatic tolerance and 24-hour urinary norepinephrine. METHODS: The study was a longitudinal observation carried out in Maringá - PR, embracing 71 patients, recruited from July, 2004 to December, 2005, evaluated before surgery and six months post-operatively. Forty two (42) women and 29 men were investigated, with age varying from 18 to 66 years old (median = 36 years old) and body mass index (BMI) varying from 37.1 to 56.2 kg/m2 (median = 41.9 kg/m2). Out of the total, 28 presented arterial hypertension. Patients diagnosed as diabetics were not included. The analysis of the time domain measures of heart rate variability, by using 24-hour Holter recordings, head-up tilt testing (HUT) and urinary 24-hour norepinephrine assay was performed during both phases of the study. Fasting plasma glucose and insulin, lipid profile, high sensitivity C-reactive protein, fibrinogen and quality of life were also evaluated by applying the SF-36 questionnaire, all before surgery and post-operatively. RESULTS: Six months after surgery, the average of weight loss was 25.46% and the waist circumference reduction was 20.4%. The mean of NN interval showed a significant increase (p<0,001), thus denoting a significant reduction of sinusal rate. The measures of heart rate variability, that is, SDNN, SDANN, SDNN index, pNN50 and rMSSD, showed significant increase (p<0.001, p<0.001, p=0.002 and p=0.002, respectively). Men presented greater increase of SDNN and SDANN than women (p=0,006 and p=0,007, respectively). Age was a significant factor for the evolution of SDNN index (p=0.015) and rMSSD (p=0.002) with a lower increase according to the aging process. The waist circumference reduction presented better correlation with heart rate variability increase than weight loss and BMI reduction. After surgery, no patient showed new symptom of orthostatic intolerance. The vasovagal response to HUT did not present a significant difference between both phases of the study. Dysautonomic response occurred just in two cases, after surgery, not allowing the evaluation of that kind of response. There was no case of symptomatic orthostatic hypotension. There was a significant reduction of asymptomatic orthostatic hypotension cases, with odds ratio of 0.10 (p=0.030) after surgery, in relation to the pre-operative phase. There was not a difference of urinary 24-hour norepinephrine in the period investigated. Fasting plasma glucose and insulin reduced while lipid profile improved and high sensitivity C-reactive protein reduced, without changing the fibrinogen. Quality of life improved. CONCLUSION: Gastric bypass changed the autonomic modulation, increasing the parasympathetic activity on sinus node, which was denoted by an increase in the heart rate variability. The change occurred without clinical worse in orthostatic tolerance and without increase in the susceptibility to vasovagal syncope.

Na África subsaariana, as serpentes do gênero Bitis são de extrema importância, pois suas vítimas apresentam sintomas como dano local, hemorragia e uma severa hipotensão. Este trabalho identificou moléculas capazes de inibir a atividade da enzima conversora de angiotensina I (ECA) presentes no veneno de quatro serpentes do gênero Bitis. Para isto, as porções de baixa massa molecular desses 4 venenos foram fracionadas em RP-HPLC e as frações com boa inibição sobre a atividade da ECA foram analisadas por espectrometria de massas. Foram identificados 34 oligopeptídeos ricos em prolina (PRO), sendo 8 sintetizados e suas constantes de inibição (Ki) determinadas. Em testes com substratos naturais da ECA, angiotensina I e bradicinina, foi constatada a maior inibição da hidrólise da angiotensina I por quatro PROs. Todos os PROs in vivo reduziram a pressão arterial, e seis deles aumentaram a frequência cardíaca em ratos Wistar. Com isto, conclui-se que existem toxinas no veneno de serpentes do gênero Bitis responsáveis pela hipotensão. / In the sub-saharian Africa, snakes from the Bitis genus are of extreme medical importance, since its victims show symptoms as local tissue damage, hemorrhage and a severe hypotension. This work identified molecules that inhibit the angiotensin I converting enzyme (ACE) in the venom of 4 snakes from the Bitis genus. The low molecular portions of the venom of these snakes were fractionated in RP-HPLC and the fractions that efficiently inhibited the ACE activity were analyzed by mass spectrometry. 34 proline-rich oligopeptides were identified, 8 of them synthesized and had their inhibition constants (Ki) determined. In tests using natural substrates of ACE, angiotensin I and bradykinin, the angiotensin I hydrolysis were better inhibited by four PROs. In vivo tests results showed that all PROs decreased the mean arterial pressure and six of them increased the heart rate. Therefore, we can conclude that there are toxins present in the venom of Bitis capable of cause hypotension.

Cannabinoid (CB) receptors have been found in most vertebrates that have been studied. The location of various CB receptors in the body and brain are known, but their physiological functions are not fully understood. The effects CBs have on the cardiovascular system have been of growing interest in recent years. Increasing reports from emergency departments and law enforcement agencies detail acute cardiovascular and psychological effects from synthetic CB intoxication, such as JWH-018. This major health concern is substantiated by governmental agencies like the CDC and NIDA. This pilot study investigates the acute toxic effects of the synthetic CB, JWH-018, on the cardiovascular and neuroendocrine systems in Ictalurus punctatus (channel catfish). Research in organisms besides the traditional mammal models can provide new insights into CB function and physiology. Ictalurus punctatus lend multiple benefits as a model organism that permits researchers to investigate in vivo effects of both cardiovascular and neuroendocrine systems without much influence from traditional sampling methods, and further more provide ample size and tissue to perform specific cardiovascular experiments. Multiple methods were used to assess cardiovascular function and sympathetic nervous system activation. Two different doses, low (500 µg/kg) and high 1,500 µg/kg, of JWH-018 were evaluated in the study. Delivery of JWH-018, via dorsal aorta cannulation, was administered to channel catfish in order to measure cardiovascular functions and sample blood. Plasma levels of the hypothalamus-pituitary-adrenal/interrenal (HPA/I) biomarkers; ACTH, cortisol, epinephrine, and norepinephrine, were measured using ELISAs. Myocardial and neural tissue was collected after the exposures for rt-PCR analysis on β2 adrenergic and glucocorticoid receptor density change. Acute exposure of JWH-018 in undisturbed channel catfish yielded several findings: (1) High dose of JWH-018 was responsible for cardio depressor effects in catfish with a tendency to produce tachycardia, (2) rt-PCR results showed a 2.7 fold increase of glucocorticoid receptor mRNA density in catfish cardiomyocytes when exposed to each dose of JWH-018, (3) Catfish plasma ACTH levels were increased with high doses of JWH-018, while plasma cortisol was increased by low doses. Channel catfish is an excellent animal model to examine the effects of synthetic cannabinoids and cardiovascular function. Acute exposures to high levels of JWH-018 appear to produce cardiovascular dysfunction providing evidence that substantiates emergency department reports, in addition yields novel information about the interaction of CBs exposure and the increase of glucocorticoid receptors levels on cardiomyocytes. The channel catfish is a new animal model that can aid in further investigations of CB exposure and multiple physiological functions for health and toxicology studies. With relatively easy adjustments from this pilot study, the effects on CBs can be monitored on Ictalurus punctatus with confident results concerning human health.

Perioperative hypotension (PH), commonly a side effect of anesthesia,is one of the main mortality causes during the 30 posterior days of asurgical procedure. Novel research lines propose combining machinelearning algorithms with the Arterial Blood Pressure (ABP) waveform tonotify healthcare professionals about the onset of a hypotensive event withtime advance and prevent its occurrence. Nevertheless, ABP waveformsare heterogeneous among patients, consequently, a general model maypresent different predictive capabilities per individual. This project aimsat improving the performance of an artificial neural network (ANN) topredict hypotension events with time advance by applying personalizedmachine learning techniques, like data grouping and domain adaptation. Wehypothesize its implementation will allow us to cluster patients with similardemographic and ABP discriminative characteristics and tailor the modelto each specific group, resulting in a worst overall but better individualperformance. Results present a slight but not clinical significant improvementwhen comparing AUROC values between the group-specific and the generalmodel. This suggests even though personalization could be a good approach todealing with patient heterogeneity, the clustering algorithm presented in thisthesis is not sufficient to make the ANN clinically feasible. / Perioperativ hypotoni (PH), vanligtvis en sidoeffekt av anestesi, är en av dehuvudsakliga dödsorsakerna under de första 30 dagarna efter ett kirurgiskt ingrepp. Nya forskningslinjer föreslår att kombinera maskininlärningsalgo-ritmer med vågformen av det arteriella blodtrycket (ABP) för att förvarna sjukvårdspersonalen om uppkomsten av en hypotensiv episod, and därmedförhindra förekomsten. ABP-vågformen är dock heterogen bland patienter,så en allmän modell kan ha olik prediktiv förmåga för olika individer.I det här projektet används personaliserade maskininlärningstekniker, somdatagruppering och domänanpassning, för att försöka förbättra ett artificielltneuralt nätverk (ANN) som förutspår hytotensiva episoder. Vår hypotes är attimplementeringen kommer låta oss klustra patienter med liknande demografioch ABP-karakteristik för att skräddarsy modellen till varje specifik grupp,vilket leder till en sämre övergripande men bättre individuell prestanda. Resultaten visar små men inte kliniskt signifikanta förbättringar när AUROC-värden jämförs mellan den gruppspecifika och den allmänna modellen. Detta tyder på att även fast personalisering kan vara en bra tillnärmning till patientersheterogenitet, är inte klusteralgoritmen som presenteras här tillräcklig förklinisk användning av ANN.

Fundação de Apoio a Pesquisa e à Inovação Tecnológica do Estado de Sergipe - FAPITEC/SE / Physical exercise acts positively against the related risk factors for systemic arterial hypertension, a chronic and non-communicable disease that affects, approximately, 30% of the world population. Even though there are numerous studies that investigated the physiological responses of the exercise in this population, studying the "dose response" of its fractionation throughout the day becomes necessary, allowing new prescription possibilities. Therefore, this study aimed to evaluate ambulatory blood pressure kinetics after a fractionation of concurrent exercise session, as well as the nitric oxide bioavailability in hypertensive middle-aged women. In this way, eleven hypertensive middle-aged women (57.45 ±5.13 years) voluntarily participated of this study and underwent three experimental sessions and one control day (CS). In the morning (MS) and night (NS) sessions, the exercise was fully paid up in the morning and evening, respectively. In fractionized session (FS), it held 50% of the volume in the morning and the remaining 50% on the night shift. It was found that the MS provided greater decay and lower blood pressure reactivity (p<0.05) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) 1h post-exercise, when compared to CS. The MS was also more effective in post-exercise hypotension for SBP than NS and FS, and promoted greater attenuation to pressure reactivity (p<0.05) than the other sessions. By analyzing the ambulatory blood pressure kinetic following the exercise, it was shown that the FS promoted lowest area under the blood pressure curve (p<0.05) for the SBP, DBP and MAP during sleep, as well as greater nitric oxide bioavailability (p<0.05) than the other sessions. In this sense, it is concluded that the FS was more effective in lower BP values at 24 hours following the exercise that other sessions, although this reduction has not been observed acutely, as observed after MS. / O exercício físico pode atuar positivamente contra os agravos correlatos à hipertensão arterial sistêmica, doença crônica e não-transmissível que incide aproximadamente 30% da população mundial. Embora existam evidências suficientes sobre as respostas fisiológicas do exercício físico nesta população, estudar a dose-resposta do seu fracionamento ao longo do dia se faz necessária, permitindo novas possibilidades para a prescrição do exercício físico. Assim, o objetivo deste estudo foi avaliar as respostas pressóricas, em até 24h, após o fracionamento de uma sessão de exercício concorrente, bem como a biodisponibilidade do óxido nítrico em mulheres hipertensas. Para tanto, participaram do presente estudo 11 mulheres hipertensas de meia-idade (57,45 ±5,13 anos) submetidas a 3 sessões experimentais e um dia controle (SC). Nas sessões manhã (SM) e noite (SN), o exercício foi realizado integralmente pela manhã e pela noite, respectivamente. Na sessão fracionada (SF), realizou-se 50% do volume pela manhã e os demais 50% no turno da noite. Verificou-se que a SM proporcionou maior decaimento e menor reatividade pressórica (p<0,05) para a pressão arterial sistólica (PAS) e para pressão arterial diastólica (PAD) 1h após o exercício, quando comparada à SC. A SM também foi mais eficiente em promover hipotensão pós-exercício para a PAS que a SN e a SF, além de promover maior atenuação à reatividade pressórica (p<0,05) que as demais sessões. Ao analisar a cinética pressórica nas 24h subsequentes ao exercício, foi evidenciado que a SF promoveu menor área abaixo da curva pressórica (p<0,05) para a PAS, PAD e PAM no período do sono, além de maior biodisponibilidade (p<0,05) do óxido nítrico que as demais sessões. Neste sentido conclui-se que que a SF foi mais eficaz em promover reduções pressóricas nas 24h subsequentes à prática de exercício físico que as demais sessões, ainda que esta redução não tenha sido evidenciada no período de 1h pós-exercício, como observada após a SM.

This thesis describes a novel method to reversibly and safely block nerve conduction using a low frequency alternating current (LFAC) waveform at 1 Hz applied through a bipolar extrafascicular electrode. This work follows up on observations made on excised mammalian peripheral nerves and earthworm nerve cords. An<i> in-situ</i> electrophysiology setup was used to assess the LFAC<br>waveform on propagating action potentials (APs) within the cervical vagus nerve in anaesthetized Sprague-Dawley rats (n = 12). Two sets of bipolar cuff or hook electrodes were applied unilaterally to the cervical vagus nerve, which was crushed rostral to the electrodes to exclude reflex effects<br>on the animal. Pulse stimulation was applied to the rostral electrode, while the LFAC conditioning waveform was applied to the caudal electrode. The efferent volley, if unblocked, elicits acute bradycardia and hypotension. The degree of block of the vagal stimulation induced bradycardia<br>was used as a biomarker. Block was assessed by the ability to reduce the bradycardic drive by monitoring the heart rate (HR) and blood pressure (BP) during LFAC alone, LFAC with vagal stimulation, and vagal stimulation alone. LFAC applied via a hook electrode (n = 7) achieved 86.6 +/- 11% block at current levels 95 +/- 38 uAp (current to peak). When applied via a cuff electrode (n = 5) 85.3 +/- 4.60% block was achieved using current levels of 110 +/- 65 uAp. Furthermore, LFAC was explored on larger vagal afferent fibers in larger human sized nerve bundles projecting to effects mediated by a reflex. The effectiveness of LFAC was assessed in an <i>in-situ</i> electrophysiological setup on the left cervical vagus in anaesthetized domestic swine (n = 5). Two bipolar cuff electrodes were applied unilaterally to the cervical vagus nerve, which was crushed caudal to the electrodes to eliminate cardiac effects. A tripolar extrafascicular cuff electrode was placed most rostral on the nerve for recording of propagating APs induced by<br>electrical stimulation and blocked via the LFAC waveform.<br>Standard pulse stimulation was applied to the left cervical vagus to induce the Hering-Breuer reflex. If unblocked, the activation of the Hering-Breuer reflex would cause breathing to slow down and potentially cease. Block was quantified by the ability to reduce the effect of the Hering-Breuer<br>reflex by monitoring the breathing rate during LFAC alone, LFAC and vagal stimulation, and vagal stimulation alone. LFAC achieved 87.2 +/- 8.8% (n = 5) block at current levels of 0.8 +/- 0.3 mAp. Compound nerve action potentials (CNAP) were monitored directly. They show changes<br>in nerve activity during LFAC, which manifests itself as the slowing and amplitude reduction of components of the CNAPs. Since the waveform is balanced, all forward reactions are reversed, leading to a blocking method that is similar in nature to DC block without the potential issues of<br>toxic byproduct production. These results suggest that LFAC can achieve a high degree of nerve block in both small and large nerve bundles, resulting in the change in behavior of a biomarker, <i>in-vivo </i>in the mammalian nervous system at low amplitudes of electrical stimulation that are within the water window of the electrode.<br>

Volume overload is a common feature in patients on haemodialysis (HD). This contributes significantly to the cardiovascular disease burden seen in these patients. Clinical assessments of the volume state are often inaccurate. Techniques such as interdialytic blood pressure, relative blood volume monitoring, bioimpedance are available to improve clinical effectives. However all these techniques exhibit significant shortcomings in their accuracy, reliability and applicability at the bed side. We evaluated the usefulness of a dual compartment monitoring technique using Continuous Segmental Bioimpedance Spectroscopy (CSBIS) and Relative Blood Volume (RBV) as a tool to assess hydration status and determine dry weight. We also sought to evaluate the role of Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP) as a volume marker in dialysis patients. The Retrospective analysis of a historical cohort (n = 376, 55 Diabetic) showed a significant reduction in post-dialysis weights in the first three months of dialysis (72.5 to 70kg, p<0.027) with a non-significant increase in weight between months 6-12. The use of anti-hypertensive agents reduced insignificantly in the first 3 months, increased marginally between months 3-6 and significantly increased over the subsequent 6 months. The residual urea clearance (KRU) fell and dialysis times increased. The cohort was very different to that dialysing at Tassin and showed a dissociation between weight reduction and BP control. This may relate to occult volume overload. CSBIS-RBV monitoring in 9 patients with pulse ultrafiltration (pulse UF) showed distinct reproducible patterns relating to extra cellular fluid (ECF) and RBV rebound. An empirical Refill Ratio was then used to define the patterns of change and this was related to the state of their hydration. A value closer to unity was consistent with the attainment of best achievable target weight. The refill ratio fell significantly between the first (earlier) and third (last) rebound phase (1.97 ± 0.92 vs 1.32 ± 0.2). CSBIS monitoring was then carried out in 31 subjects, whilst varying dialysate composition, temperature and patient posture to analyse the effects of these changes on the ECF trace and to ascertain whether any of these interventions can trigger a change in the slope of the ECF trace distinct to that caused by UF. Only, isovolemic HD caused a change in both RBV and ECF in some patients that was explained by volume re-distribution due to gravitational shifts, poor vascular reactivity, sodium gradient between plasma and dialysate and the use of vasodilating antihypertensive agents. This has not been described previously. These will need to be explored further. The study did demonstrate a significant lack of comparability of absolute values of RECF between dialysis sessions even in the same patient. This too has not been described previously. This is likely to be due to subtle changes in fluid distribution between compartments. Therefore a relative changes must be studied. This sensitivity to subtle changes may increase the usefulness of the technique for ECF tracking through dialysis. The potential of dual compartment monitoring to track volume changes in real time was further explored in 29 patients of whom 21 achieved weight reductions and were able to be restudied. The Refill Ratio decreased significantly in the 21 patients who had their dry weights reduced by 0.95 ± 1.13 kg (1.41 ± 0.25 vs 1.25 ± 0.31). Blood pressure changes did not reach statistical significance. The technique was then used to examine differences in vascular refill between a 36oC and isothermic dialysis session in 20 stable prevalent patients. Pulse UF was carried out in both these sessions. There were no significant differences in Refill Ratios, energy removed and blood pressure response between the two sessions. The core temperature (CT) of these patients was close to 36oC and administering isothermic HD did not confer any additional benefit. Mean BNP levels in 12 patients during isovolemic HD and HD with UF did not relate to volume changes. ANP concentrations fell during a dialysis session in 11 patients from a mean 249 ± 143 pg/ml (mean ± SD) at the start of dialysis to 77 ± 65 pg/ml at the end of the session (p<0.001). During isolated UF levels did not change but fell in the ensuing sham phase indicating a time lag between volume loss and decreased generation. (136±99 pg/ml to 101±77.2 pg/ml; p<0.02) In a subsequent study ANP concentrations were measured throughout dialysis and in the post-HD period for 2 hours. A rebound in ANP concentration was observed occurring at around 90 min post-HD. The degree of this rebound may reflect the prevailing fluid state and merit further study. We have shown the utility of dual compartment monitoring with CSBIS-RBV technique and its potential in assessing volume changes in real time in haemodialysis patients. We have also shown the potential of ANP as an independent marker of volume status in the same setting. Both these techniques merit further study.