Reflex syncope : an integrative physiological approach

Síncope, a forma mais comum de perda temporária de consciência é responsável por até 5% das idas aos serviços de emergência e até 3% dos internamentos hospitalares. É um problema médico frequente, com múltiplos gatilhos, incapacitante, potencialmente perigoso e desafiante em termos diagnósticos e terapêuticos. Assim, é necessária uma anamnese detalhada para primeiro estabelecer a natureza da perda de consciência, mas, após o diagnóstico, as medidas terapêuticas existentes são pouco eficazes. Embora a fisiopatologia da síncope vasovagal ainda não tenha sido completamente esclarecida, alguns mecanismos subjacentes foram já desvendados. Em última análise, a síncope depende de uma falha transitória na perfusão cerebral pelo que qualquer factor que afecte a circulação sanguínea cerebral pode determinar a ocorrência de síncope. Assim, o objectivo do presente estudo é caracterizar o impacto hemodinâmico e autonómico nos mecanismos subjacentes à síncope reflexa, para melhorar o diagnóstico, o prognóstico e a qualidade de vida dos doentes e dos seus cuidadores. Para isso, desenhámos e implementámos novas ferramentas matemáticas e computacionais que permitem uma avaliação autonómica e hemodinâmica integrada, de forma a aprofundar a compreensão do seu envolvimento nos mecanismos de síncope reflexa. Além disso, refinando a precisão do diagnóstico, a sensibilidade e a especificidade do teste de mesa de inclinação (“tilt test”), estabelecemos uma ferramenta preditiva do episódio iminente de síncope. Isso permitiu-nos estabelecer alternativas de tratamento eficazes e personalizadas para os doentes refractários às opções convencionais, sob a forma de um programa de treino de ortostatismo (“tilt training”), contribuindo para o aumento da sua qualidade de vida e para a redução dos custos directos e indirectos da sua assistência médica. Assim, num estudo verdadeiramente multidisciplinar envolvendo doentes com síncope reflexa refractária à terapêutica, conseguimos demonstrar uma assincronia funcional das respostas reflexas autonómicas e hemodinâmicas, expressas por um desajuste temporal entre o débito cardíaco e as adaptações de resistência total periférica, uma resposta baroreflexa atrasada e um desequilíbrio incremental do tónus autonómico que, em conjunto, poderão resultar de uma disfunção do sistema nervoso autónomo que se traduz por uma reserva simpática diminuída. Igualmente, desenhámos, testámos e implementámos uma plataforma computacional e respectivo software associado - a plataforma FisioSinal –incluindo novas formas, mais dinâmicas, de avaliação integrada autonómica e hemodinâmica, que levaram ao desenvolvimento de algoritmos preditivos para a estratificação de doentes com síncope. Além disso, na aplicação dessas ferramentas, comprovámos a eficácia de um tratamento não invasivo, não disruptivo e integrado, focado na neuromodulação das variáveis autonómicas e cardiovasculares envolvidas nos mecanismos de síncope. Esta terapêutica complementar levou a um aumento substancial da qualidade de vida dos doentes e à abolição dos eventos sincopais na grande maioria dos doentes envolvidos. Em conclusão, o nosso trabalho contribuiu para preencher a lacuna entre a melhor informação científica disponível e sua aplicação na prática clínica, sustentando-se nos três pilares da medicina translacional: investigação básica, clínica e comunidade.Syncope, the most common form of transient loss of consciousness, accounts for up to 5% of emergency room visits and up to 3% of hospital admissions. It is a frequent medical problem with multiple triggers, potentially dangerous, incapacitating, and challenging to diagnose. Therefore, a detailed clinical history is needed first to establish the nature of the loss of consciousness. However, after diagnosis, the therapeutic measures available are still very poor. Although the exact pathophysiology of vasovagal syncope remains to be clarified, some underlying mechanisms have been unveiled, dependent not only on the cause of syncope but also on age and various other factors that affect clinical presentation. Ultimately, syncope depends on a failure of the circulation to perfuse the brain, so any factor affecting blood circulation may determine syncope occurrence. Thus, the purpose of the present study is to understand the impact of the hemodynamic and autonomic functions on reflex syncope mechanisms to improve patients diagnose, prognosis and general quality of life. Bearing that in mind, we designed and implemented new mathematical and computational tools for autonomic and hemodynamic evaluation, in order to deepen the understanding of their involvement in reflex syncope mechanisms. Furthermore, by refining the diagnostic accuracy, sensitivity and specificity of the head-up tilt-table test, we established a predictive tool for the impending syncopal episode. This allowed us to establish effective and personalised treatment alternatives to patient’s refractory to conventional options, contributing to their increase in the quality of life and a reduction of health care and associated costs. In accordance, in a truly multidisciplinary study involving reflex syncope patients, we were able to show an elemental functional asynchrony of hemodynamic and autonomic reflex responses, expressed through a temporal mismatch between cardiac output and total peripheral resistance adaptations, a deferred baroreflex response and an unbalanced, but incremental, autonomic tone, all contributing to autonomic dysfunction, translated into a decreased sympathetic reserve. Through the design, testing and implementation of a computational platform and the associated software - FisioSinal platform -, we developed novel and dynamic ways of autonomic and hemodynamic evaluation, whose data lead to the development of predictive algorithms for syncope patients’risk stratification. Furthermore, through the application of these tools, we showed the effectiveness of a non-invasive, non-disruptive and integrated treatment, focusing on neuromodulation of the autonomic and cardiovascular variables involved in the syncope mechanisms, leading to a substantial increase of quality of life and the abolishment of syncopal events in a vast majority of the enrolled patients. In conclusion, our work contributed to fill the gap between the best available scientific information and its application in the clinical practice by tackling the three pillars of translational medicine: bench-side, bedside and community

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 165, March 1977

This bibliography lists 198 reports, articles, and other documents introduced into the NASA scientific and technical information system in February 1977

Determination and evaluation of clinically efficient stopping criteria for the multiple auditory steady-state response technique

Background: Although the auditory steady-state response (ASSR) technique utilizes objective statistical detection algorithms to estimate behavioural hearing thresholds, the audiologist still has to decide when to terminate ASSR recordings introducing once more a certain degree of subjectivity. Aims: The present study aimed at establishing clinically efficient stopping criteria for a multiple 80-Hz ASSR system. Methods: In Experiment 1, data of 31 normal hearing subjects were analyzed off-line to propose stopping rules. Consequently, ASSR recordings will be stopped when (1) all 8 responses reach significance and significance can be maintained for 8 consecutive sweeps; (2) the mean noise levels were ≤ 4 nV (if at this “≤ 4-nV” criterion, p-values were between 0.05 and 0.1, measurements were extended only once by 8 sweeps); and (3) a maximum amount of 48 sweeps was attained. In Experiment 2, these stopping criteria were applied on 10 normal hearing and 10 hearing-impaired adults to asses the efficiency. Results: The application of these stopping rules resulted in ASSR threshold values that were comparable to other multiple-ASSR research with normal hearing and hearing-impaired adults. Furthermore, in 80% of the cases, ASSR thresholds could be obtained within a time-frame of 1 hour. Investigating the significant response-amplitudes of the hearing-impaired adults through cumulative curves indicated that probably a higher noise-stop criterion than “≤ 4 nV” can be used. Conclusions: The proposed stopping rules can be used in adults to determine accurate ASSR thresholds within an acceptable time-frame of about 1 hour. However, additional research with infants and adults with varying degrees and configurations of hearing loss is needed to optimize these criteria

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 125

This special bibliography lists 323 reports, articles, and other documents introduced into the NASA scientific and technical information system in January 1974

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 128, May 1974

This special bibliography lists 282 reports, articles, and other documents introduced into the NASA scientific and technical information system in April 1974

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

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

Aerospace medicine and biology. A continuing bibliography with indexes, supplement 186

This bibliography lists 159 reports, articles, and other documents introduced into the NASA Scientific and Technical Information System in October 1978

Aerospace Medicine and Biology. A continuing bibliography with indexes

This bibliography lists 244 reports, articles, and other documents introduced into the NASA scientific and technical information system in February 1981. Aerospace medicine and aerobiology topics are included. Listings for physiological factors, astronaut performance, control theory, artificial intelligence, and cybernetics are included