Autonomisen hermoston toimintakokeiden vaikutukset sydämen repolarisaatioon

The autonomic nervous system is an important modulator of ventricular repolarization and arrhythmia vulnerability. This study explored the effects of cardiovascular autonomic function tests on repolarization and its heterogeneity, with a special reference to congenital arrhythmogenic disorders typically associated with stress-induced fatal ventricular arrhythmias. The first part explored the effects of standardized autonomic tests on QT intervals in a 12-lead electrocardiogram and in multichannel magnetocardiography in 10 healthy adults. The second part studied the effects of deep breathing, Valsalva manouvre, mental stress, sustained handgrip and mild exercise on QT intervals in asymptomatic patients with LQT1 subtype of the hereditary long QT syndrome (n=9) and in patients with arrhythmogenic right ventricular dysplasia (ARVD, n=9). Even strong sympathetic activation had no effects on spatial QT interval dispersion in healthy subjects, but deep respiratory efforts and Valsalva influenced it in ways that were opposite in electrocardiographic and magnetocardiographic recordings. LQT1 patients showed blunted QT interval and sinus nodal responses to sympathetic challenge, as well as an exaggerated QT prolongation during the recovery phases. LQT1 patients showed a QT interval recovery overshoot in 2.4 ± 1.7 tests compared with 0.8 ± 0.7 in healthy controls (P = 0.02). Valsalva strain prolonged the T wave peak to T wave end interval only in the LQT1 patients, considered to reflect the arrhythmogenic substrate in this syndrome. ARVD patients showed signs of abnormal repolarization in the right ventricle, modulated by abrupt sympathetic activation. An electrocardiographic marker reflecting interventricular dispersion of repolarization was introduced. It showed that LQT1 patients exhibit a repolarization gradient from the left ventricle towards the right ventricle, significantly larger than in controls. In contrast, ARVD patients showed a repolarization gradient from the right ventricle towards the left. Valsalva strain amplified the repolarization gradient in LQT1 patients whereas it transiently reversed it in patients with ARVD. In conclusion, intrathoracic volume and pressure changes influence regional electrocardiographic and magnetocardiographic QT interval measurements differently. Especially recovery phases of standard cardiovascular autonomic functions tests and Valsalva manoeuvre reveal the abnormal repolarization in asymptomatic LQT1 patients. Both LQT1 and ARVD patients have abnormal interventricular repolarization gradients, modulated by abrupt sympathetic activation. Autonomic testing and in particular the Valsalva manoeuvre are potentially useful in unmasking abnormal repolarization in these syndromes.Autonominen, eli tahdosta riippumaton hermosto osallistuu moniin elimistön säätelytoimintoihin, vaikuttaen suoraan myös sydämeen. Autonominen hermosto jaetaan sympaattiseen hermostoon, joka aktivoituu äkillisissä elimistön kriisitilanteissa kuten vihastumisen, stressin ja rasituksen yhteydessä, sekä parasympaattiseen hermostoon, joka puolestaan toimii vilkkaammin elimistön lepotilassa. Äkillisesti lisääntynyt sympaattisen hermoston aktiivisuus lisää vakavien rytmihäiriöiden vaaraa mm. kasvattamalla ohimenevästi sydämen sähköiseen toipumisvaiheen (repolarisaatioon) keston alueellisia eroja. Tämän ilmiön merkitys korostuu tietyissä vakaville rytmihäiriöille altistavissa perinnöllisissä taudeissa, joissa repolarisaatio on valmiiksi poikkeava. Näille taudeille on tunnusomaista henkeä uhkaavan rytmihäiriön ilmaantumisen riski tilanteissa joissa autonomisen hermoston toiminta muuttuu äkillisesti. Väitöskirjatutkimuksessa selvitettiin vakioitujen autonomisen hermoston toimintakokeiden vaikutuksia sydämen repolarisaatioon, mittaamalla monikanavaisesta sydänsähkökäyrästä (EKG) repolarisaatiota kuvaavaa QT-aikaa lyönti lyönniltä. Erityisesti tutkittiin testisarjan (syväänhengityskoe, Valsalvan koe, henkinen stressitesti, isometrinen puristuskoe, kevyt rasitus) vaikutuksia QT-aikaan kahdessa perinnöllisessä rytmihäiriösairaudessa; 1-tyypin pitkä-QT oireyhtymässä (LQT1) ja oikean kammion arytmogeenisessä dysplasiassa (ARVD). LQT1-potilailla syketaajuuden nousu ja QT-ajan lyheneminen olivat normaalia vaimeampia sympaattiseen aktivaation aikana, ja tunnusomaista oli QT-ajan poikkeava piteneminen testien palautumisvaiheissa. Lisäksi Valsalvan kokeen ponnistusvaihe pidensi ohimenevästi T-aallon huipusta T-aallon loppuun mitattua aikaintervallia, mikä katsotaan olevan rytmihäiriöriskiä parhaiten kuvaava EKG-ilmiö tässä oireyhtymässä. ARVD-potilailla havaittiin merkkejä poikkeavasta oikean kammion repolarisaatiosta, ja sen muuttumisesta sympaattisen aktivaation vaikutuksesta. Tutkimuksessa esitettiin lisäksi uusi tapa kuvata repolarisaation epäyhtenäisyyttä, arvioimalla EKG:n avulla sydämen oikean ja vasemman kammion välistä repolarisaatiogradienttia. Gradientti oli normaalia suurempi ja suunnaltaan vasemmalta oikealle LQT1-potilailla, mutta päinvastainen eli oikealta vasemmalle ARVD-potilailla. Valsalvan kokeen ponnistusvaihe korosti entisestään gradienttia LQT1-potilailla ja käänsi ohimenevästi sen suuntaa ARVD-potilailla. Autonomisen hermoston testit ja niistä erityisesti Valsalvan koe osoittautuivat käyttökelpoiseksi poikkeavan repolarisaation paljastamisessa LQT1- ja ARVD-potilailla. Kuvatuista menetelmistä saattaa jatkossa olla apua näiden sairauksien hoitolinjauksissa ja rytmihäiriöriskin arvioimisessa

Magnetic-Stimulation-Related Physiological Artifacts in Hemodynamic Near-Infrared Spectroscopy Signals

Peer reviewe

Unique Exercise Lactate Profile in Muscle phosphofructokinase Deficiency (Tarui Disease); Difference Compared with McArdle Disease

Introduction: Glycogen storage disease V (GSDV, McArdle disease) and GSDVII (Tarui disease) are the most common of the rare disorders of glycogen metabolism. Both are associated with low lactate levels on exercise. Our aim was to find out whether lactate response associated with exercise testing could distinguish between these disorders. Methods: Two siblings with Tarui disease, two patients with McArdle disease and eight healthy controls were tested on spiroergometric exercise tests with follow-up of venous lactate and ammonia. Results: A late increase of lactate about three times the basal level was seen 10-30 min after exercise in patients with Tarui disease being higher than in McArdle disease and lower than in the controls. Ammonia was increased in Tarui disease. Discussion: Our results suggest that follow-up of lactate associated with exercise testing can be utilized in diagnostics to distinguish between different GSD diseases.Peer reviewe

24-hour ambulatory blood pressure and cryptogenic ischemic stroke in young adults

AbstractBackground In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in these patients. Thus, we aimed to compare ambulatory blood pressure (ABP) profiles between young patients with a recent cryptogenic ischemic stroke (CIS) and stroke-free controls.Patients and Methods In this substudy of the international multicenter case–control study SECRETO (NCT01934725), 24-hour ambulatory blood pressure monitoring (ABPM) was performed in consecutive 18–49-year-old CIS patients and stroke-free controls. The inclusion criteria were met by 132 patients (median age, 41.9 years; 56.1% males) and 106 controls (41.9 years; 56.6% males). We assessed not only 24-hour, daytime, and nighttime ABP but also hypertension phenotypes and nocturnal dipping status.Results 24-hour and daytime ABP were higher among controls. After adjusting for relevant confounders, a non-dipping pattern of diastolic blood pressure (DBP) was associated with CIS in the entire sample (odds ratio, 3.85; 95% confidence interval, 1.20–12.42), in participants without antihypertensives (4.86; 1.07–22.02), and in participants without a patent foramen ovale (PFO) (7.37; 1.47–36.81). After excluding patients in the first tertile of the delay between the stroke and ABPM, a non-dipping pattern of DBP was not associated with CIS, but a non-dipping pattern of both systolic BP and DBP was (4.85; 1.37–17.10). In participants with a PFO and in those without hypertension by any definition, no associations between non-dipping patterns of BP and CIS emerged.Conclusions Non-dipping patterns of BP were associated with CIS in the absence of a PFO but not in the absence of hypertension. This may reflect differing pathophysiology underlying CIS in patients with versus without a PFO. Due to limitations of the study, results regarding absolute ABP levels should be interpreted with caution.Key MessagesNocturnal non-dipping patterns of blood pressure were associated with cryptogenic ischemic stroke except in participants with a patent foramen ovale and in those without hypertension by any definition, which may indicate differing pathophysiology underlying cryptogenic ischemic stroke in patients with and without a patent foramen ovale.It might be reasonable to include ambulatory blood pressure monitoring in the diagnostic work-up for young patients with ischemic stroke to detect not only the absolute ambulatory blood pressure levels but also their blood pressure behavior