203 research outputs found

    Central and Peripheral Chemoreflex Function in the Supine and Upright Postures in Women throughout the Menstrual Cycle with a Comparison to Men

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    The primary purpose of the study was to examine sex differences and menstrual cycle time-points on chemoreflex function during supine and 70o upright (HUT) positions during: 1) normoxia, 2) hypercapnia (5% CO2), or 3) hyperoxia (100% O2). Women were tested during the early-follicular phase (EF; days 2-5) and the mid-luteal phase (ML; days 18-24). Compared to baseline, men and women had lower cardiac output index (Qi), mean arterial pressure (MAP), cerebrovascular resistance index, and respiratory rate during HUT. In response to hypercapnia during HUT (compared to supine), men had an augmented increase in MAP, while all groups had an augmented increase in ventilation suggesting sexually dimorphic interactions between the baroreflex and central chemoreflex. In response to hyperoxia during HUT, men and women displayed an attenuated increase of total peripheral resistance index and an attenuated decrease of Qi suggesting upright posture activated peripheral chemoreceptors

    Trigonometric Regressive Spectral Analysis Reliably Maps Dynamic Changes in Baroreflex Sensitivity and Autonomic Tone: The Effect of Gender and Age

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    BACKGROUND: The assessment of baroreflex sensitivity (BRS) has emerged as prognostic tool in cardiology. Although available computer-assisted methods, measuring spontaneous fluctuations of heart rate and blood pressure in the time and frequency domain are easily applicable, they do not allow for quantification of BRS during cardiovascular adaption processes. This, however, seems an essential criterion for clinical application. We evaluated a novel algorithm based on trigonometric regression regarding its ability to map dynamic changes in BRS and autonomic tone during cardiovascular provocation in relation to gender and age. METHODOLOGY/PRINCIPAL FINDINGS: We continuously recorded systemic arterial pressure, electrocardiogram and respiration in 23 young subjects (25+/-2 years) and 22 middle-aged subjects (56+/-4 years) during cardiovascular autonomic testing (metronomic breathing, Valsalva manoeuvre, head-up tilt). Baroreflex- and spectral analysis was performed using the algorithm of trigonometric regressive spectral analysis. There was an age-related decline in spontaneous BRS and high frequency oscillations of RR intervals. Changes in autonomic tone evoked by cardiovascular provocation were observed as shifts in the ratio of low to high frequency oscillations of RR intervals and blood pressure. Respiration at 0.1 Hz elicited an increase in BRS while head-up tilt and Valsalva manoeuvre resulted in a downregulation of BRS. The extent of autonomic adaption was in general more pronounced in young individuals and declined stronger with age in women than in men. CONCLUSIONS/SIGNIFICANCE: The trigonometric regressive spectral analysis reliably maps age- and gender-related differences in baroreflex- and autonomic function and is able to describe adaption processes of baroreceptor circuit during cardiovascular stimulation. Hence, this novel algorithm may be a useful screening tool to detect abnormalities in cardiovascular adaption processes even when resting values appear to be normal

    Clinical Implications for Carotid Body Neuromodulation

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    Funding Information: This study was partially supported by the GlaxoSmithKline Bioelectronics R&D ?Innovation Challenge. JS and BM were supported by a contract and a Ph.D. Grant from the Portuguese Foundation for Science and Technology Reference CEECIND/02428/2018 and PD/BD/128336/2017, respectively. This study received funding from the Fundação para a Ciência e Tecnologia (FCT) (UIDB/05704/2020).Chronic carotid sinus nerve (CSN) electrical modulation through kilohertz frequency alternating current improves metabolic control in rat models of type 2 diabetes, underpinning the potential of bioelectronic modulation of the CSN as a therapeutic modality for metabolic diseases in humans. The CSN carries sensory information from the carotid bodies, peripheral chemoreceptor organs that respond to changes in blood biochemical modifications such as hypoxia, hypercapnia, acidosis, and hyperinsulinemia. In addition, the CSN also delivers information from carotid sinus baroreceptors—mechanoreceptor sensory neurons directly involved in the control of blood pressure—to the central nervous system. The interaction between these powerful reflex systems—chemoreflex and baroreflex—whose sensory receptors are in anatomical proximity, may be regarded as a drawback to the development of selective bioelectronic tools to modulate the CSN. Herein we aimed to disclose CSN influence on cardiovascular regulation, particularly under hypoxic conditions, and we tested the hypothesis that neuromodulation of the CSN, either by electrical stimuli or surgical means, does not significantly impact blood pressure. Experiments were performed in Wistar rats aged 10–12 weeks. No significant effects of acute hypoxia were observed in systolic or diastolic blood pressure or heart rate although there was a significant activation of the cardiac sympathetic nervous system. We conclude that chemoreceptor activation by hypoxia leads to an expected increase in sympathetic activity accompanied by compensatory regional mechanisms that assure blood flow to regional beds and maintenance of hemodynamic homeostasis. Upon surgical denervation or electrical block of the CSN, the increase in cardiac sympathetic nervous system activity in response to hypoxia was lost, and there were no significant changes in blood pressure in comparison to control animals. We conclude that the responses to hypoxia and vasomotor control short-term regulation of blood pressure are dissociated in terms of hypoxic response but integrated to generate an effector response to a given change in arterial pressure.publishersversionpublishe

    CARDIO-RESPIRATORY INTERACTION AND ITS CONTRIBUTION IN SYNCOPE

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    A hypothetical causal link between ventilatory regulation of carbon dioxide anddevelopment of syncope during orthostatic challenges is reduction in arterial partialpressure of carbon dioxide and resultant reduction in cerebral blood flow. We performedtwo experiments to investigate the ventilatory sensitivity to carbon dioxide and factorsaffecting cerebral autoregulation (CA). We also studied the nonlinear phase couplingbetween cardio-respiratory parameters before syncope.For experiment one, in 30 healthy adults, we stimulated chemo and baro reflexesby breathing either room-air or room-air with 5 percent carbon dioxide in a pseudorandom binary sequence during supine and 70 degree head up tilt (HUT). Six subjectsdeveloped presyncope during tilt.To determine whether changes in ventilatory control contribute to the observeddecrease in PaCO2 during HUT, we assessed ventilatory dynamic sensitivity to changesin PaCO2 during supine and 70 degrees HUT. The sensitivity of the ventilatory controlsystem to perturbations in end tidal carbon dioxide increased during tilt.To investigate nonlinear phase coupling between cardio-respiratory parametersbefore syncope, bispectra were estimated and compared between presyncopal andnon-presyncopal subjects. Our results indicate that preceding presyncope, nonlinearphase coupling is altered by perturbations to baro and chemo reflexes.To investigate the effects of gender in CA, we selected 10 men and 10age-matched women and used spectral analysis to compare differences in CA betweenmen and women. Our results showed that gender-related differences in CA did exist andgender may need to be considered as a factor in investigating CA.To investigate the influence of induced hypocapnia on CA in absence ofventilatory variability, we performed experiment two in which subjects were randomlyassigned to a Control (under normocapnia) or Treatment (under hypocapnia) group. Bothgroups voluntarily controlled their breathing pattern yet two groups breathed in air withdifferent levels of carbon dioxide. Our results show that changes in mean blood pressureat middle cerebral artery level were less transferred into mean cerebral blood flow in theTreatment group than in the Control group, suggesting better CA under hypocapniarelative to under normocapnia

    Autonomic Cardiovascular Control in Health and Disease

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    Effects of SIDS risk factors and hypoxia on cardiovascular control in infants

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    Background and aims. Sudden infant death syndrome (SIDS) is a rare lethal event occurring in 0.1 to 0.3 of infants. In Finland, 10 to 20 infants die from SIDS annually. Research has defined many risk factors for SIDS, but the cascade leading to death remains unexplained. Cardiovascular recordings of infants succumbing to SIDS, as well as animal models, suggest that the final sequelae involve cardiovascular collapse resembling hypotensive shock. There is also evidence of previous hypoxia in SIDS infants. In animal studies, vestibulo-mediated cardiovascular control has been shown to be important in hypotensive shock. Hence, we hypothetized that SIDS victims may have impaired vestibulo-mediated cardiovascular control, possibly due to previous hypoxic episodes. In this thesis, we studied cardiovascular control, and especially vestibulo-mediated cardiovascular control in infants with known risk factors for SIDS at 2 to 4 months of age when the risk for SIDS is highest. Study subjects. A full polysomnographic recording with continuous blood pressure (BP) measurement was performed in 50 infants at 2-4 months of age: 20 control infants, nine infants with univentricular heart (UVH) suffering from chronic hypoxia, 10 infants with bronchopulmonary dysplasia (BPD) with intermittent postnatal hypoxic events, and 11 infants whose mothers had smoked during pregnancy, and thus had been exposed to intrauterine hypoxia and nicotine, were studied. In addition, 20 preterm infants were studied at the gestational age of 34-39 weeks to evaluate developmental aspects of cardiovascular control during head-up tilt test and vestibular stimulus. Methods. Linear side motion and 45° head-up tilt tests were performed in quiet non-rapid eye movement sleep (NREM). Heart rate (HR) and BP responses were analysed from the tests without signs of subcortical or cortical arousal. In addition, HR variability during NREM sleep was assessed. As a general marker of cardiovascular reactivity, HR response to spontaneous arousal from NREM sleep was also evaluated. Results.Side motion test. In the side motion test, control infants presented a biphasic response. First, there was a transient increase in HR and BP. This was followed by a decrease in BP to below baseline, and a return to baseline in HR. All other infant groups showed altered responses. UVH infants and preterm infants near term age had markedly reduced responses. Infants with BPD presented with variable responses: some responded similarly to controls, whereas others showed no initial increase in BP, and the following BP decrease was more prominent. Infants with intrauterine exposure to cigarette smoke showed flat initial BP responses, and the following decrease was more prominent, similarly to a subgroup of BPD infants. Tilt test. Control infants presented with a large variability in BP responses to head-up tilting. On average, systolic BP remained, at first, close to baseline, and diastolic BP increased, after which both decreased and remained below baseline even at the end of the tilt test. On average, HR showed a biphasic response with an initial increase followed by a decrease to below and, finally, a return to baseline. UVH infants showed a similar BP response, but their HR response was tachycardic. Preterm infants with BPD presented with an even greater variability in their BP responses to head-up tilts than control infants, but the overall response as a group did not differ from that of the controls. The tilt response of infants exposed to maternal cigarette smoking during pregnancy did not markedly differ from the control response. Preterm infants near term age showed attenuated responses in both cardiovascular measures, together with greater inter-subject variability compared to the control infants. Discussion. In conclusion, the studied infants with SIDS risk factors showed altered vestibulo-mediated cardiovascular control during the linear side motion test and head-up tilt test. The findings support our initial hypothesis that some infants with SIDS risk factors have defective vestibulo-mediated cardiovascular control, which may lead to death in life-threatening situations.Kätkytkuolemat ovat harvinaisia, mutta ne ovat edelleen suurin yksittäinen syy täysiaikaisena syntyneiden imeväisten kuolemaan. Suomessa kätkytkuolemaan menehtyy vuosittain 10-20 lasta. Kätkytkuoleman syytä ei tiedetä. Epidemiologisten tutkimusten avulla kätkytkuoleman riskitekijät tunnetaan hyvin; näitä ovat mm. vatsallaan nukkuminen, äidin raskaudenaikainen tupakointi ja keskosuus. Selällään nukuttamisen yleistymisen myötä kätkytkuolemien määrä on vähentynyt olennaisesti. Koe-eläintöissä ja muutamassa kätkytkuoleman aikaisessa seurantanauhoituksessa on viitteitä siitä, että kätkytkuoleman mekanismi todennäköisesti muistuttaa verenvuotosokin loppuvaiheen kaltaista verenkiertoelimistön toiminnan romahtamista. Koe-eläintöiden perusteella tällaisessa sokkitilanteessa tasapainotumakevälitteinen verenkierron säätely on tärkeää. Tämän tutkimuskokonaisuuden pääolettaman mukaan kätkytkuolleilla on puutteellinen tasapainotumakevälitteinen sykkeen ja verenpaineen säätely. Koska kätkytkuolleilla on myös todettu merkkejä hapenpuutteesta ennen kuolemaa, voi poikkeavan tasapainotumakevälitteisen verenkierron säätelyn syynä olla edeltänyt hapenpuute: riskiryhmistä esimerkiksi keskosilla lyhytkestoiset hapenpuutejaksot ja äidin raskaudenaikaiselle tupakoinnille altistuneilla lapsilla pitkäaikainen lievä hapenpuute sikiöaikana. Myös pitkäaikaisesta syntymän jälkeisestä hapenpuutteesta kärsivillä yksikammiosydämisillä imeväisillä on todettu äkillisiä, kätkytkuoleman kaltaisia kuolemia. Tutkimme imeväisen verenkierron säätelyä unen aikana rekisteröimällä verenkiertovasteita sivuttaissiirto- ja kippilavatestille täysiaikaisilla imeväisillä sekä imeväisillä, joilla on yllämainittuja kätkytkuoleman riskitekijöitä tai hapenpuutetta. Unirekisteröinti tehtiin yhteensä 70 imeväiselle. 2-4 kuukauden korjatussa iässä tutkittiin 20 täysiaikaista verrokkia, 10 bronkopulmonaalisesta dysplasiasta kärsivää keskosta, 9 yksikammiosydämistä imeväistä sekä 11 imeväistä, joiden äidit tupakoivat raskauden aikana. Lisäksi tutkimme 20 keskosta 34-39 raskausviikon iässä sykkeen ja verenpaineen säätelyn kehityksen kartoittamiseksi. Sivuttaissiirtotesti sekä 45° kippilavatesti pää ylöspäin tehtiin rauhallisessa ei-REM-unessa. Terveiden täysiaikaisten verrokkien verenpaine- ja sykevasteita käytettiin vertailukohtana muiden ryhmien vasteita arvioitaessa. Syke- ja verenpainevasteet arvioitiin testeistä, joissa ei ollut viitettä havahtumisesta tai heräämisestä. Sydämen sykkeen vaihtelevuutta ja spontaanin heräämisen aiheuttamaa sykevastetta käytettiin kuvaamaan yleistä verenkiertoelimistön säätelyn herkkyyttä. Sivuttaissiirtotestissä verrokit reagoivat kaksivaiheisella syke- ja verenpainevasteella. Sekä verenpaine että syke nousivat aluksi, jonka jälkeen verenpaine laski alle lähtötason ennen paluuta lähtötasoon, ja syke palasi lähtötasoon. Muissa tutkituissa ryhmissä vasteet poikkesivat normaalivasteista. Yksikammiosydänlapsilla sekä lähellä laskettua aikaa tutkituilla keskosilla syke- ja verenpainevasteet sivuttaissiirrolle olivat hyvin vaimeat. Puolet bronkopulmonaalisesta dysplasiasta kärsivistä imeväisistä reagoi samoin kuin verrokit, mutta puolella verenpaineen nousu puuttui ja sitä seurannut verenpaineen lasku oli selvästi normaalia syvempi. Myös imeväisillä, joiden äidit olivat tupakoineet raskauden aikana, verenpaineen alkunousu puuttui ja sitä seurannut verenpaineen lasku oli verrokkeja syvempi. Kippilavatestissä täysiaikaisten verrokkien verenpainevasteet olivat hyvin vaihtelevat. Keskimäärin testin alussa systolinen verenpaine pysyi ennallaan ja diastolinen nousi. Testin jatkuessa molemmat laskivat alle lähtötason, jossa ne pysyivät vielä testin lopettamisen jälkeenkin. Verrokkien sykevasteet olivat selkeästi yhtenevämmät ja vaste oli kaksivaiheinen: alun sykkeen nousua seurasi sykkeen lasku alle lähtötason ja paluu takaisin lähtötasoon. Yksikammiosydänlasten verenpainevasteet olivat verrokkien kaltaiset, mutta heidän sykkeensä pysyi korkeana koko testin ajan. Bronkopulmonaalisesta dysplasiasta kärsivien imeväisten verenpainevasteissa oli vielä voimakkaampaa vaihtelua kuin verrokkien vasteissa, mutta ryhmänä heidän vasteensa ei eronnut verrokeista. Raskaudenaikaiselle tupakoinnille altistuneiden imeväisten verenkiertovasteet eivät eronneet verrokeista. Lähellä laskettua aikaa tutkittujen keskosten syke- ja verenpainevasteissa oli suurta vaihtelua verrattuna täysiaikaisiin verrokkeihin, mutta ryhmänä verenkiertovasteet olivat vaimeammat kuin verrokeilla. Tässä tutkimuksessa todettiin poikkeava tasapainotumakevälitteinen verenkierron säätely imeväisillä, joilla on yllämainittuja kätkytkuoleman riskitekijöitä ja edeltäneitä hapenpuutejaksoja. Tutkimustulokset tukevat etukäteisolettamustamme, että heikentynyt tasapainotumakevälitteinen verenkierron säätely imeväisillä voi olla osaltaan johtamassa kätkytkuolemaan henkeä uhkaavassa tilanteessa

    Sex Hormones and Sympathetic Nerve Activity

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    The purpose of this thesis was to test the hypothesis that changes in circulating sex hormone levels are associated with changes in muscle sympathetic nerve activity. The hypothesis was tested through the comparison of low- (early follicular [EF]) and high-hormone (midluteal [ML]) phases of the menstrual cycle and of hormonal contraceptive use (low hormone [LH] versus high hormone [HH]). The microneurography technique was used to compare both the frequency and size of bursts in muscle sympathetic nerve activity (MSNA) at baseline and during two sympatho-excitatory maneuvers: baroreceptor unloading elicited through lower body negative pressure, and chemoreflex stimulation elicited through a hypoxic-hypercapnic end-inspiratory apnea. Sympathetic responses to chemoreflex stimulation were also compared between women and men. All associations between MSNA and hormone phases occurred similarly between users and non-users of hormonal contraceptives. At baseline, MSNA was relatively elevated during the high hormone phases (ML and HH), at which point baseline sympathetic activity was similar to that observed in men. However, stimulation of the chemoreflex resulted in greater sympathetic activation during the low hormone phases (EF and LH) relative to the high hormone phases. Further, this hormone phase effect was mediated largely by greater increases in burst size, rather than the burst frequency component. This may indicate that central integration sites for MSNA are affected by circulating sex hormone levels. Finally, the sympathetic responses to baroreceptor unloading were graded to reductions in stroke volume, which, in turn, were affected by hormone levels. However, no evidence was observed to suggest a change in the central integration of baroreceptor afferent input occurred across phases of the menstrual cycle or hormonal contraceptive use in terms of baroreflex function. Together, these studies confirm that sympathetic nerve activity at baseline and sympathetic recruitment during chemoreflex stimulation are affected by hormone phase, while baroreceptor-mediated responses are not affected by the transition from low (EF and LH) to high hormone phases (ML and HH)

    Beyond the Baroreflex: A New Measure of Autonomic Regulation Based on the Time-Frequency Assessment of Variability, Phase Coherence and Couplings

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    For decades the role of autonomic regulation and the baroreflex in the generation of the respiratory sinus arrhythmia (RSA) - modulation of heart rate by the frequency of breathing - has been under dispute. We hypothesized that by using autonomic blockers we can reveal which oscillations and their interactions are suppressed, elucidating their involvement in RSA as well as in cardiovascular regulation more generally. R-R intervals, end tidal CO2, finger arterial pressure, and muscle sympathetic nerve activity (MSNA) were measured simultaneously in 7 subjects during saline, atropine and propranolol infusion. The measurements were repeated during spontaneous and fixed-frequency breathing, and apnea. The power spectra, phase coherence and couplings were calculated to characterise the variability and interactions within the cardiovascular system. Atropine reduced R-R interval variability (p \u3c 0.05) in all three breathing conditions, reduced MSNA power during apnea and removed much of the significant coherence and couplings. Propranolol had smaller effect on the power of oscillations and did not change the number of significant interactions. Most notably, atropine reduced R-R interval power in the 0.145–0.6 Hz interval during apnea, which supports the hypothesis that the RSA is modulated by a mechanism other than the baroreflex. Atropine also reduced or made negative the phase shift between the systolic and diastolic pressure, indicating the cessation of baroreflex-dependent blood pressure variability. This result suggests that coherent respiratory oscillations in the blood pressure can be used for the non-invasive assessment of autonomic regulation
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