Browsing by Author "Rocha, Isabel"
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- Acute vagal modulation of electrophysiology of the atrial and pulmonary veins increases vulnerability to atrial fibrillationPublication . Oliveira, Mario; da Silva, M. Nogueira; Geraldes, Vera; Xavier, Rita; Laranjo, Sergio; Silva, Vitor; Postolache, Gabriela; Ferreira, Rui; Rocha, IsabelVagal activity is thought to influence atrial electrophysiological properties and play a role in the initiation and maintenance of atrial fibrillation (AF). We evaluated the effects of acute vagal stimulation on atrial conduction, refractoriness of atrial and pulmonary veins (PVs) and inducibility of AF. An open-chest epicardial approach was performed in New Zealand White rabbits with preserved autonomic innervation. Atrial electrograms were obtained with four unipolar electrodes placed epicardially along the atria (n = 22) and an electrode adapted to the proximal left PV (n = 10). The cervical vagus nerve was stimulated with bipolar platinum electrodes (20 Hz). Epicardial activation was recorded in sinus rhythm, and effective refractory periods (ERPs), dispersion of refractoriness and conduction times from high-lateral right atrium (RA) to high-lateral left atrium (LA) and PVs assessed at baseline and during vagal stimulation. Burst pacing (50 Hz, 10 s), alone or combined with vagal stimulation, was applied to the right (RAA) and left atrial appendage (LAA) and PVs to induce AF. At baseline, ERPs were lower in PVs than in LA and LAA, but did not differ significantly from RA and RAA, and there was a significant delay in the conduction time from RA to PVs compared with the activation time from RA to LA (P < 0.01). During vagal stimulation, ERP decreased significantly at all sites, without significant differences in the dispersion of refractoriness, and the atrial conduction times changed from 39 ± 19 to 49 ± 9 ms (RA to PVs; n.s.) and from 14 ± 7 to 28 ± 12 ms (RA to LA; P = 0.01). Induction of AF was reproducible in 50% of cases with 50 Hz and in 82% with 50 Hz combined with vagal stimulation (P < 0.05). During vagal stimulation, AF cycle length decreased at all sites, and AF duration changed from 1.0 ± 0.9 to 14.0 ± 10.0 s (P < 0.01), with documentation of PV tachycardia in three cases. In 70% of the animals, AF ceased immediately after interruption of vagal stimulation. We conclude that in the intact rabbit heart, vagal activity prolongs interatrial conduction and shortens atrial and PV ERP, contributing to the vulnerability to the induction and maintenance of AF. This model may be useful in the assessment of the autonomic influence in the mechanisms underlying AF.
- Amlodipine effects on vasomotion in rabbit externalPublication . Delgado, Esmeralda; Marques-Neves, Carlos; Rocha, Isabel; Sales-Luís, José; Silva-Carvalho, LuísBackground In order to understand the role of ocular blood flow in normal and pathological conditions, knowledge of the pharmacological control mechanisms involved in the ocular vascular bed is essential. The present study was designed to investigate the reactivity of the rabbit external ophthalmic artery and its collaterals to amlodipine, in order to answer two questions: (1) What are amlodipine effects upon perfusion pressure and spontaneous oscillations in the in situ perfused rabbit eyes? (2) Can intraarterial amlodipine counteract ET-1 induced vasoconstriction? Methods Rabbit external ophthalmic arteries (n=12) in a head-mounted preparation were cannulated and perfused with warmed tyrode. Vasomotor response curves to intraarterial injections of amlodipine 3 mg/ml followed by phenylephrine 250 μg (group A, n=6) and to amlodipine 3 mg/ml after an intraarterial injection of endothelin-1 (ET-1) 27 μg/ml (group B, n=6) were obtained. For statistical analysis, the paired t-test and Fourier analysis of frequency spectrums of spontaneous oscillations were used. Results Before any drug administration, spontaneous oscillations were observed in the 12 rabbit models. In group A, amlodipine elicited vasodilation and a decrease in frequency and amplitude of the oscillations. In group B, ET-1 induced an increase in vasoconstrictor tone and vasomotion became more evident.With amlodipine after ET-1, we obtained vasodilation and abolition of the vasospasm. Conclusions Our study has two main conclusions: (1) amlodipine, an L-type calcium channel blocker, caused intense vasodilation and decreased both frequency and amplitude of the spontaneous oscillations observed in the rabbit external ophthalmic artery and its collaterals, and (2) when we applied amlodipine in arteries previously contracted by the administration of ET-1, vascular resistance greatly decreased and spontaneous oscillations were abolished. Since ET-1 levels are increased in several ischemic ocular diseases, amlodipine might be beneficial in these patients, allowing a protective action against vasospasm.
- Autonomic function evaluation in an intermittent lead exposure animal modelPublication . Shvachiy, Liana; Geraldes, Vera; Carvalho, Mafalda; Rocha, IsabelLead (Pb) is a toxic metal, which widespread use has resulted in environmental contamination, human exposure and significant public health problems. The autonomic nervous system, being a homeostatic controller, is impaired in acute and chronic lead exposure. In fact, sympathoexcitation associated to hypertension and tachypnea has been described together with baroreflex and chemoreflex dysfunction. However, up to date, no studies described the autonomic effects of an intermittent low-level lead exposure. In the present work, we addressed in vivo, autonomic behaviour in rats under chronic Pb exposure (control) and in rats under intermittent Pb exposure. For that, arterial blood pressure (BP) and ECG were recorded in 28 weeks old animal and low frequencies (LF) and high frequencies (HF) were determined (to estimate sympathetic and parasympathetic activities) using FisioSinal software with Wavelet module. Preliminary results: Rats intermittently exposed to lead showed a significant decrease in systolic BP (126 ± 4 vs 144 ± 3 mmHg) with no significant changes in LF, HF and LF/HF bands (1.5 ± 0.3 vs 1.7 ± 0.5 mmHg2, 1.9 ± 0.7 vs 2.8 ± 1.2 bpm2 and 1.2 ± 0.4 vs 1.1 ± 0.3 mmHg2/bpm2, respectively) when compared to chronically Pb exposed rats. Our data suggests that the autonomic dysfunction induced by lead exposure is similar in a chronic and intermittent Pb exposure. Nevertheless, it seems that an intermittent exposure was no effect on systolic BP values. The present study brings new insights on the environmental factors that influence autonomic and cardiovascular systems during development, which can help apprise public policy strategies to prevent and control the adverse effects of Pb toxicity.
- Autonomic nervous system education in Europe: EAN/EFAS/INUS survey on curricula and skills in autonomic medicine of European neurology residents and consultantsPublication . Reis‐Carneiro, Diogo; Skoric, Magdalena Krbot; Habek, Mario; Adamec, Ivan; Calandra‐Buonaura, Giovanna; Cortelli, Pietro; van Dijk, J. Gert; Falup‐Pecurariu, Cristian; Guaraldi, Pietro; Hilz, Max J.; Iodice, Valeria; Jordan, Jens; Rocha, Isabel; Struhal, Walter; Terkelsen, Astrid Juhl; Thijs, Roland; Tijero, Beatriz; Berger, Thomas; Rektorova, Irena; Moro, Elena; Traon, Anne Pavy‐Le; Wenning, Gregor; Panicker, Jalesh N.; Fanciulli, AlessandraBackground and purpose: Centers for training in autonomic nervous system (ANS) disorders are not widely available and the recent coronavirus 2019 pandemic temporarily reduced training opportunities in autonomic medicine across European countries. Here we evaluated the current state of education, clinical skills and postgraduate educational preferences on ANS disorders of European neurology residents and consultants. Methods: A 23-item questionnaire was developed and distributed online amongst European neurology residents and consultants via mailing lists of the European Academy of Neurology. The questions assessed demographics, current training opportunities and learning preferences in ANS disorders. Six multiple-choice questions were used to self-evaluate knowledge of ANS disorders. Results: In all, 285 individuals answered the survey (60% female, mostly 25-34 years of age). All respondents considered clinical autonomic skills necessary for good clinical neurological practice, and 92% would like to increase their ANS knowledge. Female respondents and those who trained in Southern/Eastern/Greater Europe more frequently judged ANS skills important for clinical practice than male respondents (p = 0.012) and respondents from Northern/Western Europe (p = 0.011). Female and younger respondents felt less confident in managing ANS disorders (p = 0.001 and p < 0.001, respectively). Respondents below 45 years of age (p < 0.001) and those with lower confidence in managing ANS disorders (p = 0.004) were more likely to recommend that ANS education is embedded in the residency curriculum. Conclusions: Most European neurology residents and consultants reported a need for more autonomic education, with additional gender, age and regional differences. These findings underscore the importance of increasing the educational content on autonomic medicine in European medical and postgraduate curricula.
- Cardiometabolic risk in childhood : could bilirubin act as a circadian clock-related mediator via autonomic dysfunction?Publication . Meira e Cruz, Miguel; Rocha, Isabel; Bruni, OlivieroThe interesting paper from Yu and colleagues on the association of neonatal serum bilirubin and childhood hypertension recently published in Plos One, flagged up a plausible role of bilirubin as a mediator of hypertension in later life. This is a highly important topic since hypertension, a main cause of cardiometabolic associated morbidity and mortality, may affect 2% to 4% of children. Bilirubin is a toxic endproduct of heme catabolism in the body, commonly seen in newborns and causing jaundice. It is detoxified mainly in the liver by means of several steps involving circadian regulated enzymatic processes. A balanced autonomic output to the liver is crucial for maintenance of the circadian rhythmicity that ensures the normal function of liver metabolic enzymes and glucose level.
- Chronic depression of hypothalamic paraventricular neuronal activity produces sustained hypotension in hypertensive ratsPublication . Geraldes, Vera; Gonçalves-Rosa, Nataniel; Liu, Beihui; Paton, Julian F. R.; Rocha, IsabelChanges in the sympathetic nervous system are responsible for the initiation, development and maintenance of hypertension. An important central sympathoexcitatory region is the paraventricular nucleus (PVN) of the hypothalamus, which may become more active in hypertensive conditions, as shown in acute studies previously. Our objective was to depress PVN neuronal activity chronically by the overexpression of an inwardly rectifying potassium channel (hKir2.1), while evaluating the consequences on blood pressure (BP) and its reflex regulation. In spontaneously hypertensive rats (SHRs) and Wistar rats (WKY) lentiviral vectors (LVV-hKir2.1; LV-TREtight-Kir-cIRES-GFP5 4 × 10(9) IU and LV-Syn-Eff-G4BS-Syn-Tetoff 6.2 × 10(9) IU in a ratio 1:4) were stereotaxically microinjected bilaterally into the PVN. Sham-treated SHRs and WKY received bilateral PVN microinjections of LVV-eGFP (LV-Syn-Eff-G4BS-Syn-Tetoff 6.2 × 10(9) IU and LV-TREtight-GFP 5.7 × 10(9) IU in a ratio 1:4). Blood pressure was monitored continuously by radio-telemetry and evaluated over 75 days. Baroreflex gain was evaluated using phenylephrine (25 μg ml(-1), i.v.), whereas lobeline (25 μg ml(-1), i.v.) was used to stimulate peripheral chemoreceptors. In SHRs but not normotensive WKY rats, LVV-hKir2.1 expression in the PVN produced time-dependent and significant decreases in systolic (from 158 ± 3 to 132 ± 6 mmHg; P < 0.05) and diastolic BP (from 135 ± 4 to 113 ± 5 mmHg; P < 0.05). The systolic BP low-frequency band was reduced (from 0.79 ± 0.13 to 0.42 ± 0.09 mmHg(2); P < 0.05), suggesting reduced sympathetic vasomotor tone. Baroreflex gain was increased and peripheral chemoreflex depressed after PVN microinjection of LVV-hKir2.1. We conclude that the PVN plays a major role in long-term control of BP and sympathetic nervous system activity in SHRs. This is associated with reductions in both peripheral chemosensitivity and respiratory-induced sympathetic modulation and an improvement in baroreflex sensitivity. Our results support the PVN as a powerful site to control BP in neurogenic hypertension.
- Clinical autonomic nervous system laboratories in Europe: a joint survey of the European Academy of Neurology and the European Federation of Autonomic SocietiesPublication . Habek, Mario; Leys, Fabian; Krbot Skorić, Magdalena; Reis Carneiro, Diogo; Calandra‐Buonaura, Giovanna; Camaradou, Jennifer; Chiaro, Giacomo; Cortelli, Pietro; Falup‐Pecurariu, Cristian; Granata, Roberta; Guaraldi, Pietro; Helbok, Raimund; Hilz, Max J.; Iodice, Valeria; Jordan, Jens; Kaal, Evert C. A.; Kamondi, Anita; Pavy Le Traon, Anne; Rocha, Isabel; Sellner, Johann; Senard, Jean Michel; Terkelsen, Astrid; Wenning, Gregor K.; Berger, Thomas; Thijs, Roland D.; Struhal, Walter; Fanciulli, Alessandra; Adamec, Ivan; Aerts, Arnaud; Canta, Leo L.R.; Delamont, Robert Shane; de Lange, Frederik; Del Sorbo, Francesca; Devigili, Grazia; Di Leo, Rita; Dinh, Trang; Fortrat, Jacques‐Olivier; Gierthmühlen, Janne; Hemels, Martin; Köhn, Julia; Krøigård, Thomas; Lipp, Axel; Maier, Andrea; Marinelli, Lucio; Mazzeo, Anna; Milenkovic, Ivan; Motyl, Maciej; Natali Sora, Maria Grazia; Navarro‐Otano, Judith; Nilsen, Kristian Bernhard; Oliveira, Mario; Omland, Petter Moe; Pelliccioni, Giuseppe; Pereon, Yann; Resch, Roland Josef; Rocchi, Camilla; Roche, Frederic; Rutten, Joost; Tijero Merino, Beatriz; Tutaj, Marcin; van der Heijden‐Montfroy, A.M.H.G.; van Hoeve, Bas J.A.; van Orshoven, Narender; Wang, Ruihao; Z’Graggen, Werner J.Background and purpose: Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology-driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences. Methods: We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web-based survey. Results: We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head-up tilt tests/laboratory/year is 105 (49-251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty-five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100-360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4-110] inpatient stays/year). Forty-one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021). Conclusions: This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.
- Clinical presentation and management strategies of cardiovascular autonomic dysfunction following a COVID‐19 infection: a systematic reviewPublication . Reis Carneiro, Diogo; Rocha, Isabel; Habek, Mario; Helbok, Raimund; Sellner, Johann; Struhal, Walter; Wenning, Gregor; Fanciulli, AlessandraBackground: Cardiovascular autonomic dysfunction may reportedly occur after a coronavirus-disease-2019 (COVID-19) infection, but the available evidence is scattered. Here we sought to understand the acute and mid-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on cardiovascular autonomic function. Methods: We performed a systematic PubMed, Embase, Web of Science, medRxiv, and bioRxiv search for cases of cardiovascular autonomic dysfunction during an acute SARS-CoV-2 infection or post-COVID-19 condition. The clinical-demographic characteristics of individuals in the acute versus post-COVID-19 phase were compared. Results: We screened 6470 titles and abstracts. Fifty-four full-length articles were included in the data synthesis. One-hundred and thirty-four cases were identified: 81 during the acute SARS-CoV-2 infection (24 thereof diagnosed by history) and 53 in the post-COVID-19 phase. Post-COVID-19 cases were younger than those with cardiovascular autonomic disturbances in the acute SARS-CoV-2 phase (42 vs. 51 years old, p = 0.002) and were more frequently women (68% vs. 49%, p = 0.034). Reflex syncope was the most common cardiovascular autonomic disorder in the acute phase (p = 0.008) and postural orthostatic tachycardia syndrome (POTS) the most frequent diagnosis in individuals with post-COVID-19 orthostatic complaints (p < 0.001). Full recovery was more frequent in individuals with acute versus post-COVID-19 onset of cardiovascular autonomic disturbances (43% vs. 15%, p = 0.002). Conclusions: There is evidence from the scientific literature about different types of cardiovascular autonomic dysfunction developing during and after COVID-19. More data about the prevalence of autonomic disorders associated with a SARS-CoV-2 infection are needed to quantify its impact on human health.
- EFAS/EAN survey on the influence of the COVID-19 pandemic on European clinical autonomic education and researchPublication . Fanciulli, Alessandra; Skorić, Magdalena Krbot; Leys, Fabian; Carneiro, Diogo Reis; Campese, Nicole; Calandra-Buonaura, Giovanna; Camaradou, Jennifer; Chiaro, Giacomo; Cortelli, Pietro; Falup-Pecurariu, Cristian; Granata, Roberta; Guaraldi, Pietro; Helbok, Raimund; Hilz, Max J.; Iodice, Valeria; Jordan, Jens; Kaal, Evert C. A.; Kamondi, Anita; Le Traon, Anne Pavy; Rocha, Isabel; Sellner, Johann; Senard, Jean Michel; Terkelsen, Astrid; Wenning, Gregor K.; Moro, Elena; Berger, Thomas; Thijs, Roland D.; Struhal, Walter; Habek, Mario; Adamec, Ivan; Aerts, Arnaud; Canta, Leo L. R.; Delamont, Robert Shane; de Lange, Frederik; Del Sorbo, Francesca; Devigili, Grazia; Di Leo, Rita; Dinh, Trang; Fortrat, Jacques-Olivier; Gierthmühlen, Janne; Hemels, Martin; Köhn, Julia; Krøigård, Thomas; Lipp, Axel; Maier, Andrea; Marinelli, Lucio; Mazzeo, Anna; Milenkovic, Ivan; Motyl, Maciej; Sora, Maria Grazia Natali; Navarro-Otano, Judith; Nilsen, Kristian Bernhard; Oliveira, Mario; Omland, Petter Moe; Pelliccioni, Giuseppe; Pereon, Yann; Resch, Roland Josef; Rocchi, Camilla; Roche, Frederic; Rutten, Joost; Tijero-Merino, Beatriz; Tutaj, Marcin; van der Heijden-Montfroy, A. M. H. G.; van Hoeve, Bas J. A.; van Orshoven, Narender; Wang, Ruihao; Z’Graggen, Werner J.Purpose: To understand the influence of the coronavirus disease 2019 (COVID-19) pandemic on clinical autonomic education and research in Europe. Methods: We invited 84 European autonomic centers to complete an online survey, recorded the pre-pandemic-to-pandemic percentage of junior participants in the annual congresses of the European Federation of Autonomic Societies (EFAS) and European Academy of Neurology (EAN) and the pre-pandemic-to-pandemic number of PubMed publications on neurological disorders. Results: Forty-six centers answered the survey (55%). Twenty-nine centers were involved in clinical autonomic education and experienced pandemic-related didactic interruptions for 9 (5; 9) months. Ninety percent (n = 26/29) of autonomic educational centers reported a negative impact of the COVID-19 pandemic on education quality, and 93% (n = 27/29) established e-learning models. Both the 2020 joint EAN-EFAS virtual congress and the 2021 (virtual) and 2022 (hybrid) EFAS and EAN congresses marked higher percentages of junior participants than in 2019. Forty-one respondents (89%) were autonomic researchers, and 29 of them reported pandemic-related trial interruptions for 5 (2; 9) months. Since the pandemic begin, almost half of the respondents had less time for scientific writing. Likewise, the number of PubMed publications on autonomic topics showed the smallest increase compared with other neurological fields in 2020-2021 and the highest drop in 2022. Autonomic research centers that amended their trial protocols for telemedicine (38%, n = 16/41) maintained higher clinical caseloads during the first pandemic year. Conclusions: The COVID-19 pandemic had a substantial negative impact on European clinical autonomic education and research. At the same time, it promoted digitalization, favoring more equitable access to autonomic education and improved trial design.
- Efficacy of cerebral autoregulation in early ischemic stroke predicts smaller infarcts and better outcomePublication . Castro, Pedro; Serrador, Jorge Manuel; Rocha, Isabel; Sorond, Farzaneh; Azevedo, ElsaBackground and purpose: Effective cerebral autoregulation (CA) may protect the vulnerable ischemic penumbra from blood pressure fluctuations and minimize neurological injury. We aimed to measure dynamic CA within 6 h of ischemic stroke (IS) symptoms onset and to evaluate the relationship between CA, stroke volume, and neurological outcome. Methods: We enrolled 30 patients with acute middle cerebral artery IS. Within 6 h of IS, we measured for 10 min arterial blood pressure (Finometer), cerebral blood flow velocity (transcranial Doppler), and end-tidal-CO2. Transfer function analysis (coherence, phase, and gain) assessed dynamic CA, and receiver-operating curves calculated relevant cut-off values. National Institute of Health Stroke Scale was measured at baseline. Computed tomography at 24 h evaluated infarct volume. Modified Rankin Scale (MRS) at 3 months evaluated the outcome. Results: The odds of being independent at 3 months (MRS 0–2) was 14-fold higher when 6 h CA was intact (Phase > 37°) (adjusted OR = 14.0 (IC 95% 1.7–74.0), p = 0.013). Similarly, infarct volume was significantly smaller with intact CA [median (range) 1.1 (0.2–7.0) vs 13.1 (1.3–110.5) ml, p = 0.002]. Conclusion: In this pilot study, early effective CA was associated with better neurological outcome in patients with IS. Dynamic CA may carry significant prognostic implications.