Baroreflex control of heart rate (HR) is impaired in diabetes mellitus. We hypothesized that diabetes mellitus induced functional changes of neural components at multiple sites within the baroreflex arc. Type 1 diabetic mice (OVE26) and FVB control mice were anesthetized. Baroreflex-mediated HR responses to sodium nitroprusside- (SNP) and phenylephrine- (PE) induced mean arterial blood pressure (MAP) changes were measured. Baroreceptor function was characterized by measuring the percent (%) change of baseline integrated aortic depressor nerve activity (Int ADNA) in response to SNP- and PE-induced MAP changes. The HR responses to electrical stimulation of the left aortic depressor nerve (ADN) and the right vagus nerve were assessed. Compared with FVB control mice, we found in OVE26 mice that (1) baroreflex-mediated bradycardia and tachycardia were significantly reduced. (2) The baroreceptor afferent function in response to MAP increase did not differ, as assessed by the parameters of the logistic function curve. But, the inhibition of Int ADNA in response to MAP decrease was significantly attenuated. (3) The maximum amplitude of bradycardic responses to right vagal efferent stimulation was augmented. (4) In contrast, the maximum amplitude of bradycardic responses to left ADN stimulation was decreased. Since Int ADNA was preserved in response to MAP increase and HR responses to vagal efferent stimulation were augmented, we conclude that a deficit of the central mediation of baroreflex HR contributes to the overall attenuation of baroreflex sensitivity in OVE26 mice. The successful conduction of physiological experiments on the ADN in OVE26 mice may provide a foundation for the understanding of cellular and molecular mechanisms of diabetes-induced cardiac neuropathy.

Interoception, the perception of the body's physiological state, is often studied in relation to emotion processing. Particularly, cardioception has been largely implicated in anxiety. Three related but distinct dimensions of interoception have recently emerged in the literature: sensibility (IS), accuracy (IAC), and awareness (IAW). Divergent findings regarding interoception and anxiety may result from lacking appreciation for interoceptive dimensions. Additionally, the role of cardiovascular afferent feedback in anxiety and interoception is largely unknown. Baroreflex sensitivity (BRS) has been implicated in interoceptive processes yet no known research directly measures this in relation to multidimensional cardioception. The present study aimed to assess the degree to which IS, IAC, IAW, and BRS predict trait anxiety at rest and during anticipatory anxiety. Results partially suggest increased IAC and BRS, but more variable IS and IAW in relation to trait anxiety. Overall, results show complex associations among factors, suggesting increased specificity among the constructs. Results highlight the importance of attention to construct validity and method variance in the study of interoceptive subdomains. Finally, the present study helps to pave the way for continued investigations concerning cardioception in enduring anxiety and the related role of the baroreflex in cardiac afferent processes. / PHD / Interoception, the perception of the body’s physiological state, is often studied in relation to emotion processing. Particularly, cardioception (the sense of cardiac activity, such as the perception of a racing heart) has been largely implicated in anxiety. Three related but distinct dimensions of interoception have recently emerged in the literature: sensibility (IS), accuracy (IAC), and awareness (IAW). Divergent findings regarding interoception and anxiety may result from lacking appreciation for interoceptive dimensions. Additionally, the role of cardiovascular feedback to the brain in anxiety and interoception is largely unknown. The baroreflex system rapidly modulates activity of the heart in accordance with short-term blood pressure changes. The sensitivity of this homeostatic baroreflex system (BRS) also plays a role in interoceptive processes, yet no known research directly measures this in relation to multidimensional cardioception. The present study aimed to assess the degree to which IS, IAC, IAW, and BRS predict dispositional anxiety at rest and during anticipatory anxiety. Results partially suggest increased IAC and BRS, but more variable IS and IAW in relation to dispositional anxiety. Overall, results show complex associations among factors, suggesting increased specificity among the variables. Results highlight the importance of attention to measurement precision and various ways to assess the dimensions of interoception. Finally, the present study helps to pave the way for continued research concerning perception of the heart’s activity in enduring anxiety and the related role of cardiovascular activity at various levels of conscious awareness. Ultimately, research on this topic is highly important for the eventual improvement of existing therapeutics for individuals regularly experiencing severe anxiety.

Maintenance of stable arterial blood pressure during orthostatic challenges is a major problem after spinal cord injury (SCI). Since early participation in rehabilitation is critically important in reducing long term morbidity, recovering the ability to regulate blood pressure during therapy is essential for individuals with SCI. The objective of our study was to investigate short term cardiovascular function of able-bodied (AB), paraplegic (PARA) and tetraplegic (TETRA) subjects in response to head up tilt (HUT) as an early indicator of autonomic damage that might forewarn of future orthostatic regulatory problems. We acquired cardiovascular variables from able-bodied (AB; n=11), paraplegic (PARA; n=5) and tetraplegic (TETRA; n=5) subjects in response to HUT. The SCI patients in both groups were in their first two months post injury. Data were recorded at rest and during 7 min each at 20??, 40??, 60?? and 80?? HUT. Techniques used to estimate regulatory capability and reflex activity included: Mean values and spectral power of heart rate (HR) and arterial blood pressure (BP), baroreflex sequence measurements and cross correlation between HR and systolic blood pressure (SBP). An index of baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), and the percentage occurrence of systolic blood pressure (BP) ramps and baroreflex sequences were calculated from baroreflex sequence measurements. The spectral power of HR and BP, the cross correlation of systolic BP and heart rate (HR) were examined in low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.4 Hz) ranges. The BRS index was significantly (p andlt; 0.05) decreased from supine to 80o HUT in AB and TETRA. This index in PARA was the lowest at each tilt position in the three groups, and decreased with tilt. The percentage of heart beats involved in systolic BP ramps and in baroreflex sequences significantly (pandlt;0.05) rose from supine to 80o HUT in AB, was relatively unchanged in PARA and declined in TETRA. Both of these indexes were significantly (pandlt;0.05) lowerin the SCI than in the AB group at each tilt level. The BEI values were greatest in AB, and declined with tilt in all groups. Spinal cord injured patients had less power of BP and HR fluctuations than AB in both LF and HF regions. The LF spectral power of BP and HR increased with tilt in AB, remained unchanged in PARA and decreased in TETRA. The HF spectral power of HR decreased in all three groups. The peak HR / BP cross correlation in the LF region was greatest in AB, and significantly (pandlt;0.05) increased during HUT in AB, remained fairly constant in PARA, and declined in TETRA. The peak cross correlation in the HF region significantly (pandlt;0.05) decreased with tilt in all groups, and the SCI group had lower values than AB at each tilt level. We conclude that both PARA and TETRA had a smaller percentage of SBP ramps, BRS, and lower BEI than AB, likely indicating decreased stimulation of arterial baroreceptors, and less engagement of feedback control. The mixed sympathetic, parasympathetic innervations of paraplegics, or their elevated HR, may contribute to their significantly lower BRS. Our data indicate that the pathways utilized to evoke baroreflex regulation of HR are compromised by SCI and this loss may be a major contributor to the decrease in orthostatic tolerance following injury.

Objective: As the multiple trigonometric regressive spectral (MTRS) analysis is extraordinary in its ability to analyze short local data segments down to 12 s, we wanted to evaluate the impact of the data segment settings by applying the technique of MTRS analysis for baroreflex sensitivity (BRS) estimation using a standardized data pool. Methods: Spectral and baroreflex analyses were performed on the EuroBaVar dataset (42 recordings, including lying and standing positions). For this analysis, the technique of MTRS was used. We used different global and local data segment lengths, and chose the global data segments from different positions. Three global data segments of 1 and 2 min and three local data segments of 12, 20, and 30 s were used in MTRS analysis for BRS. Results: All the BRS-values calculated on the three global data segments were highly correlated, both in the supine and standing positions; the different global data segments provided similar BRS estimations. When using different local data segments, all the BRS-values were also highly correlated. However, in the supine position, using short local data segments of 12 s overestimated BRS compared with those using 20 and 30 s. In the standing position, the BRS estimations using different local data segments were comparable. There was no proportional bias for the comparisons between different BRS estimations. Conclusion: We demonstrate that BRS estimation by the MTRS technique is stable when using different global data segments, and MTRS is extraordinary in its ability to evaluate BRS in even short local data segments (20 and 30 s). Because of the non-stationary character of most biosignals, the MTRS technique would be preferable for BRS analysis especially in conditions when only short stationary data segments are available or when dynamic changes of BRS should be monitored.

Abstract Neurogenic factors are known to be important in the development of hypertension. Our current knowledge of the role of autonomic nervous system in chronic hypertension is, however, limited. The purpose of the present study was to evaluate the possible abnormalities in heart rate variability (HRV) and baroreflex sensitivity (BRS) in patients with long standing systemic hypertension compared to subjects without evidence of cardiovascular disease. A particular aim was also to examine whether genetic variation in the renin-angiotensin-aldosterone system (RAS) genes have an influence on cardiovascular autonomic regulation. Case-control studies were carried out on a total of 280 normotensive and 214 hypertensive subjects drawn from a random middle-aged population originally recruited for an epidemiologic study of cardiovascular risk factors. The possible association of BRS with the genetic polymorphisms of renin-angiotensin-aldosterone system genes was studied in a cross-sectional study of 315 healthy controls. Genetic associations were also tested in a younger, independent population sample of 66 subjects. The effects of intensified antihypertensive treatment on autonomic cardiovascular control were evaluated in 33 hypertensive patients with poor blood pressure control. Wide interindividual variation in both HRV and BRS was observed in normotensive as well as hypertensive subjects. Overall HRV and autonomic responses to a change in body posture were blunted in long-standing hypertension. Decreased HRV was mainly related to elevated blood pressure and obesity. For the first time in a population-based study, it was confirmed that BRS is impaired in patients with long-standing hypertension despite adequate antihypertensive treatment. In contrast to HRV, BRS was reduced in hypertensive subjects also after adjustment for blood pressure and obesity. BRS also varied widely both between healthy and hypertensive individuals. The wide interindividual variation in the markers of autonomic cardiovascular regulation was not, however, completely explained by demographic variables, cardiovascular risk factors or lifestyle, suggesting a genetic component contributing to HRV and BRS. The polymorphism in the aldosterone synthase (CYP11B2) gene was found to strongly associate with BRS in two independent random populations of apparently healthy subjects. The association was even stronger in the younger population. On the basis of the observations made in the older population, it seems possible that women are protected against the effect of age and blood pressure on BRS and tend to maintain the genomic influence longer. Intensified antihypertensive combination therapy improved blood pressure control and caused regression of left ventricular hypertrophy, and resulted in significant improvements of HRV and BRS. The present study shows that HRV and BRS are altered in long-standing systemic hypertension. Together with age, blood pressure and obesity, genetic factors seem to be important determinants of BRS. However, abnormal autonomic cardiovascular regulation does not seem to be an irreversible phenomenon, but can be partly restored by modern combination antihypertensive therapy.

Un stress intense et répété peut être à l'origine de troubles émotionnels majeurs. Les pathologiques cardiorespiratoires liées aux troubles anxieux et dépressifs constituent un problème sanitaire de grande ampleur. Au terme d'une procédure consistant à soumettre des rats à un protocole de défaite sociale, tous les animaux présentent un profil de type anxieux 5 jours après le stress (D10). Environ la moitié des rats stressés ont montré des atteintes cardiovasculaires et respiratoires persistantes à long terme, à savoir une hyperactivité sympathique, une inhibition du baroréflexe cardiovagal et une bradypnée, à D10 mais aussi à D30 lorsque le profil anxieux avait disparu. Ces modifications s'accompagnent d'altérations cardiaques électriques (arythmies) et morphologiques (hypertrophie). Deux principales zones cérébrales à l'origine de la persistance des modifications cardiorespiratoires ont été identifiées, le noyau dorsomédian de l'hypothalamus (DMH) et le noyau du tractus solitaire (NTS). Cette population d'animaux présentant des altérations cardiorespiratoires persistantes est aussi caractérisée par un taux de BDNF sanguin faible, marqueur d'une vulnérabilité à la dépression, et par une augmentation de BDNF dans la RVL et le NTS, conséquence possible de l'existence d'un stress oxydant. L'angiotensine II semble également impliquée dans ces atteintes cardiorespiratoires. Ainsi, ce travail a permis de mettre en évidence un circuit central impliqué dans les atteintes cardiorespiratoires liés aux troubles anxiodépressifs afin d'envisager des cibles thérapeutiques plus spécifiques. / Chronic stress can cause major emotional disorders. Cardiorespiratory diseases related to anxiety and depression is a major health problem. After a social defeat paradigm, all animals exhibited an anxiety-like state five days after stress (D10). About half of the stressed rats have shown long term persistent cardiovascular and respiratory modifications, namely a sympathetic hyperactivity, an inhibition of cardiovagal baroreflex and a bradypnea, at D10 but also D30 when anxiety profile disappeared. They were associated to electric (arrhythmias) and morphologic (hypertrophy) cardiac alterations. Two main brain areas involved in the persistence of cardiorespiratory changes were identified, the dorsomedial nucleus of the hypothalamus (DMH) and the nucleus of the solitary tract (NTS). This population with persistent cardiorespiratory alterations were also characterized by a lower blood level of BDNF, a marker of vulnerability to depression, and by higher BDNF expression in the RVL and NTS. Angiotensin II may also be involved in these modifications. Thus, this study has highlighted a central pathway in cardiorespiratory modifications related to anxiety and depression to consider more specific therapeutic targets.

No description available.

Objective: As the multiple trigonometric regressive spectral (MTRS) analysis is extraordinary in its ability to analyze short local data segments down to 12 s, we wanted to evaluate the impact of the data segment settings by applying the technique of MTRS analysis for baroreflex sensitivity (BRS) estimation using a standardized data pool. Methods: Spectral and baroreflex analyses were performed on the EuroBaVar dataset (42 recordings, including lying and standing positions). For this analysis, the technique of MTRS was used. We used different global and local data segment lengths, and chose the global data segments from different positions. Three global data segments of 1 and 2 min and three local data segments of 12, 20, and 30 s were used in MTRS analysis for BRS. Results: All the BRS-values calculated on the three global data segments were highly correlated, both in the supine and standing positions; the different global data segments provided similar BRS estimations. When using different local data segments, all the BRS-values were also highly correlated. However, in the supine position, using short local data segments of 12 s overestimated BRS compared with those using 20 and 30 s. In the standing position, the BRS estimations using different local data segments were comparable. There was no proportional bias for the comparisons between different BRS estimations. Conclusion: We demonstrate that BRS estimation by the MTRS technique is stable when using different global data segments, and MTRS is extraordinary in its ability to evaluate BRS in even short local data segments (20 and 30 s). Because of the non-stationary character of most biosignals, the MTRS technique would be preferable for BRS analysis especially in conditions when only short stationary data segments are available or when dynamic changes of BRS should be monitored.

Orientador: Luiz Henrique Florindo / Banca: Diana Amaral Monteiro / Banca: Monica Jones Costa / Resumo: Os mecanismos de modulação da pressão arterial a curto prazo estão relacionados ao sistema nervoso autônomo. A primeira e mais rápida ação para o controle da pressão é feita por barorreceptores. Estes receptores detectam variações na pressão e atuam enviando informações ao sistema nervoso central (SNC), o qual desencadeia reações autonômicas que geram mudanças na frequência cardíaca (fH), na força contrátil do coração e na resistência vascular sistêmica, causando vasodilatação ou vasoconstrição, que tendem a normalizar a pressão arterial. Além da função primária do barorreflexo de manter a pressão arterial estável, uma relação inversamente proporcional entre pressão arterial e as variáveis respiratórias já foi observada em mamíferos e em anfíbios. Neste último grupo, além dessa interação entre o barorreflexo e a ventilação, o reflexo barostático também está relacionado com o sistema linfático. Há dados que também sugerem a existência dessa modulação em répteis crocodilianos. Apesar de já ter sido observada em alguns grupos de vertebrados terrestres, a correlação entre o barorreflexo e a ventilação nunca foi estudada em peixes, embora tenha sido especulada a existência da mesma devido a considerável conservação evolutiva das redes neurais que coordenam o sistema cardiorrespiratório. Neste contexto, o presente estudo investigou a existência dessa modulação barorreflexo-ventilação em uma espécie de teleósteo, a tilápia-do-nilo (O. niloticus). Para isso foram feitas aplicações... / Abstract: The mechanisms of short-term blood pressure modulation are related to the autonomic nervous system. The first and fastest action for pressure control is made by baroreceptors. These receptors detect variations in pressure and act by sending information to the central nervous system (CNS), which triggers autonomic reactions that generate changes in heart rate (fH), in the contractile force of the heart and in systemic vascular resistance, causing vasodilation or vasoconstriction, which tend to normalize blood pressure. In addition to the primary function of baroreflex to maintain stable blood pressure, an inverse relationship between blood pressure and respiratory variables has been observed in mammals and amphibians. In amphibians, the barostatic reflex is also related to the lymphatic system. There are data that also suggest the existence of this modulation in crocodilian reptiles. Even though it has been observed in some groups of terrestrial vertebrates, the correlation between baroreflex and ventilation has never been studied in fish, although it has been speculated because of the considerable evolutionary conservation of the neural networks that coordinate the cardiorespiratory system. In this context, the present study investigated the existence of this baroreflex-ventilation modulation in a teleost species, the Nile tilapia (O. niloticus). For this, we made applications of a vasoconstrictor drug, phenylephrine hydrochloride, and a vasodilator drug, sodium ... / Mestre

Baroreflex control of heart rate (HR) is impaired in human diabetes mellitus and in large experimental models. However, baroreflex impairment in diabetic mouse models and diabetes-induced remodeling of baroreflex circuitry are not well studied. We examined the impairment of baroreflex control of heart rate (HR) and assessed structural remodeling of cardiac ganglia in the streptozotocin (STZ)-induced diabetic mouse model. FVB mice were either injected with vehicle or STZ. Group 1: mice were anesthetized and the femoral artery and vein were catheterized at the 30th day after vehicle or STZ injection. On the second day after surgery, baroreflex-mediated HR responses to sodium nitroprusside (SNP) and phenylephrine (PE)-induced mean arterial blood pressure (MABP) changes were measured in conscious mice. Group 2: Fluoro-Gold was administered (i.p.) to label cardiac ganglia in each mouse at the 25th day after vehicle or STZ injection. After another five days, animals were perfused and cardiac ganglia were examined using confocal microscopy. Compared with control, we found in STZ mice: 1) the HR decreased, but MABP did not. 2) The PE-induced increases of MABP were decreased. 3) Baroreflex bradycardia was attenuated in the rapid MABP ascending phase but the steady-state ΔHR/ΔMABP was not different at all PE doses. 4) SNP-induced MABP decreases were not different. 5) Baroreflex tachycardia was attenuated. 6) The sizes of cardiac ganglia and ganglionic principal neurons were decreased. 7) The ratio of nucleus/cell body of cardiac ganglionic neurons was increased. We conclude that baroreflex control of HR is impaired in conscious STZ mice. In addition, diabetes may induce a significant structural remodeling of cardiac ganglia. Such an anatomical change of cardiac ganglia may provide new information for the understanding of diabetes-induced remodeling of the multiple components within the baroreflex circuitry.