Aerospace medicine and biology: A continuing bibliography with indexes, supplement 162, January 1977

This bibliography lists 189 reports, articles, and other documents introduced into the NASA scientific and technical information system in December 1976

EKG-parametrien käyttö kammioperäisten rytmihäiriöiden lyhyen aikavälin ennustamisessa

Malignant spontaneous ventricular arrhythmias, such as ventricular tachycardia (VT) and ventricular fibrillation (VF), are the most common trigger of sudden cardiac death (SCD) in and out of hospital. For a hospitalized patient, occurrence of such arrhythmia is a struggle of life and death where every second of oxygen deprivation, resulting from reduced blood flow, decreases chances of survival. Despite recent advances in resuscitation strategies, survival rates in in-hospital cardiac arrests remain unacceptably low. Main factors contributing to the poor prognosis are lack of patient monitoring and delay in the initiation of resuscitation. Thus, in order to increase the likelihood of successful resuscitation, or prevent the arrhythmia from happening in the first place, continuous and quantitative risk of arrhythmia assessment is required. Currently, however, cardiac monitoring is utilized to detect the onset of life threatening cardiac episodes only. Thus, development of risk indices and the study of precursors of lethal arrhythmias have great clinical value and will lead to better cardiac monitoring. In this thesis, changes in ECG signal preceding lethal cardiac arrhythmias are studied both in different patient groups and in individual patients. Furthermore, an algorithm predicting imminent ventricular tachyarrhythmias is presented. Current knowledge of underlying mechanisms of onset of ventricular arrhythmias is used to assess the risk of arrhythmia continuously during cardiac monitoring of a patient. Our approach is novel and similar assessment of such algorithm has not been published previously. A review of existing methods and applications for risk assessment of SCD with discussion of future trends and possibilities is also given.Malignit kammioperäiset rytmihäiriöt, kuten kammiotakykardia ja kammiovärinä, ovat yleisimpiä syitä sydänperäiseen äkkikuolemaan sekä sairaalassa että sen ulkopuolella. Sairaalassa kuten sen ulkopuolellakin tällaiset rytmihäiriöt ovat aina hengenvaarallisia ja pitkittyessään vähentynyt tai pysähtynyt hapenkuljetus elimistöön pienentää todennäköisyyttä selviytyä. Huolimatta viimeaikaisista ponnisteluista viiveettömän ja tehokkaamman elvytyksen eteen, sairaalassa tapahtuvien sydänkohtausten ennuste on pysynyt huonona. Tämä johtuu lähinnä viiveestä elvytyksen aloittamisessa ja monitoroinnin puutteesta, joten oleellisinta ennusteen parantamisen kannalta olisi jatkuva rytmihäiriöriskin kvantitatiivinen arviointi potilasmonitoroinnilla. Näin useat rytmihäiriöt voitaisiin estää ja alkaviin voitaisiin reagoida nopeammin. Nykyisin potilasmonitorointi on kuitenkin keskittynyt jo alkaneiden rytmihäiriöiden tunnistamiseen eikä ennustavia ratkaisuja ole tarjolla. äkillistä sydänkohtausta edeltävien ilmiöiden tutkiminen ja rytmihäiriöriskin määrittäminen kajoamattomalla potilasmonitoroinnilla ovat ensisijaisen tärkeitä, mikäli rytmihäiriöpotilaiden ennustetta halutaan parantaa sairaalaympäristössä. Tässä opinnäytteessä tutkitaan rytmihäiriöitä edeltäviä muutoksia EKG-signaalista mitattavissa parametreissa eri potilasryhmissä ja yksittäisillä potilailla. Esittelemme algoritmin, joka arvioi EKG:sta mitatuista parametreista yksittäisen potilaan riskiä rytmihäiriön käynnistymiseen. Valitsemamme lähestymistapa poikkeaa täysin olemassa olevista eikä vastaavia tuloksia ole aikaisemmin julkaistu. Algoritmin kehityksessä hyödynnetään laajasti olemassa olevaa tutkimustietoa rytmihäiriöiden käynnistymisestä ja ylläpidosta. Olemassa olevat menetelmät on esitelty laajassa kirjallisuuskatsauksessa. Opinnäytetyön lopussa algoritmin kliinistä hyödyllisyyttä ja tulevia kehitysnäkymiä on arvioitu saavutettujen tulosten valossa

Genotype-Phenotype Relationships in Long QT Syndrome : Role of Mental Stress, Adrenergic Activity and a Common KCNH2 Polymorphism

Long QT syndrome is a congenital or acquired arrhythmic disorder which manifests as a prolonged QT-interval on the electrocardiogram and as a tendency to develop ventricular arrhythmias which can lead to sudden death. Arrhythmias often occur during intense exercise and/or emotional stress. The two most common subtypes of LQTS are LQT1, caused by mutations in the KCNQ1 gene and LQT2, caused by mutations in the KCNH2 gene. LQT1 and LQT2 patients exhibit arrhythmias in different types of situations: in LQT1 the trigger is usually vigorous exercise whereas in LQT2 arrhythmia results from the patient being startled from rest. It is not clear why trigger factors and clinical outcome differ from each other in the different LQTS subtypes. It is possible that stress hormones such as catecholamines may show different effects depending on the exact nature of the genetic defect, or sensitivity to catecholamines varies from subject to subject. Furthermore, it is possible that subtle genetic variants of putative modifier genes, including those coding for ion channels and hormone receptors, play a role as determinants of individual sensitivity to life-threatening arrhythmias. The present study was designed to identify some of these risk modifiers. It was found that LQT1 and LQT2 patients show an abnormal QT-adaptation to both mental and physical stress. Furthermore, as studied with epinephrine infusion experiments while the heart was paced and action potentials were measured from the right ventricular septum, LQT1 patients showed repolarization abnormalities which were related to their propensity to develop arrhythmia during intense, prolonged sympathetic tone, such as exercise. In LQT2 patients, this repolarization abnormality was noted already at rest corresponding to their arrhythmic episodes as a result of intense, sudden surges in adrenergic tone, such as fright or rage. A common KCNH2 polymorphism was found to affect KCNH2 channel function as demonstrated by in vitro experiments utilizing mammalian cells transfected with the KCNH2 potassium channel as well as QT-dynamics in vivo. Finally, the present study identified a common β-1-adrenergic receptor genotype that is related a shorter QT-interval in LQT1 patients. Also, it was discovered that compound homozygosity for two common β-adrenergic polymorphisms was related to the occurrence of symptoms in the LQT1 type of long QT syndrome. The studies demonstrate important genotype-phenotype differences between different LQTS subtypes and suggest that common modifier gene polymorphisms may affect cardiac repolarization in LQTS. It will be important in the future to prospectively study whether variant gene polymorphisms will assist in clinical risk profiling of LQTS patients.Pitkä QT -oireyhtymä on perinnöllinen sairaus, johon liittyy vakavia sydämen rytmihäiriöitä Oireyhtymä voi tunnistamattomana tai hoitamattomana johtaa odottamattomaan äkkikuolemaan.: Suomessa arvioidaan olevan ainakin 2000 pitkä QT -potilasta. Pitkä QT -oireyhtymä johtuu sydänlihassolun poikkeavan hitaasta sähköarsytyksen jälkeisestä palautumisvaiheesta (repolarisaatiosta), joka havaitaan EKG:ssa pidentyneenä Q-aikana. Sydämen repolarisaatio perustuu kaliumkanavien toimintaan, ja kalium-ionivirrat vastaavatkin pääasiassa sydänlihassolun paluusta lepotilaan. Kaksi yleisintä pitkä QT -oireyhtymän perinnöllistä alatyyppiä johtuvat puolestaan sydänlihassolun kaliumkanavia koodittavien geenien mutaatioista. Nämä geenit ovat KCNQ1 (taudin alatyyppi LQT1) ja KCNH2 (alatyyppi LQT2). Vaikka tiedetään että toiset LQT1 ja LQT2 -potilaat saavat rytmihäiriöitä muita herkemmin, mekanismia ei vielä tiedetä. Mutta altistavissa tekijöissä on tärkeitä eroja: LQT1-potilaiden rytmihäiriöt ilmenevät useimmiten fyysisen rasituksen aikana, kun taas LQT2-potilaiden rytmihäiriöt esiintyvät äkillisen psyykkisen ärsykkeen, esimerkiksi pelästymisen, seurauksena. Väitöskirjatyössä pyrittiin selvittämään, mistä nämä erot johtuvat. Väitöskirjatyön ensimmäisessä osatyössä selvitettiin, miten terveiden koehenkilöiden, LQT1-potilaiden ja LQT2-potilaiden QT-aika eroaa voimakkaan kokeellisen psyykkisen rasituksen ja fyysisen rasituksen aikana. Sekä LQT1- että LQT2-potilailla oli pidempi QT-aika kuin kontrolleilla, mutta näitä potilasryhmiä ei kuitenkaan pystytty erottelemaan toisistaan QT-ajan perusteella. Toisessa osatyössä mitattiin kontrollien, LQT1- ja LQT2 -potilaiden sähköisten impulssien kestoa ja muotoa sydämen oikeasta kammiosta. Tuloksena havaittiin, että aktiopotentiaalin muodon perusteella LQT2-potilaat ovat herkkiä rytmihäiriöille levossa, kun taas LQT1-potilailla ilmaantui rytmihäiriöille altistava muutos vasta stressihormoni adrenaliinin vaikutuksesta. Kolmannessa osatyössä selvitettiin yleisimmän tunnetun KCNH2-polymorfismin vaikutusta kyseisen kaliumkanavan toimintaan. Havaittiin, että kanavan harvinaisempi variantti (897T) toimi heikommin kuin yleisempi muoto ja siihen liittyi myös pidempi QT-aika. Viimeisessä osatyössä määritettiin, miten kaksi yleistä β1-adrenoseptorin polymorfiaa vaikuttaa LQT1-potilaiden QT-aikaan ja rytmihäiriöherkkyyteen. Niillä potilailla, joilla oli biologisesti aktiivisempaa β1-reseptoria vastaava geenivariantti, QT-aika oli lyhempi. Potilaat, jotka kantoivat samanaikaisesti kahta aktiivista reseptorityyppiä, olivat kaikkein alttiimpia rytmihäiriöille. Väitöskirjatyössä pystyttiin siis havaitsemaan kliinisesti tärkeitä elektrofysiologisia eroja pitkä QT-oireyhtymän eri alaryhmissä. Lisäksi havaittiin, että kaliumkanavien ja beeta-adrenergisten reseptorien yleiset variantit voivat toimia pitkä QT-oireyhtymän "muuntelijageeneinä", jotka saattavat jossain määrin vaikuttaa potilaiden rytmihäiriöalttiuteen

Advances in Digital Processing of Low-Amplitude Components of Electrocardiosignals

This manual has been published within the framework of the BME-ENA project under the responsibility of National Technical University of Ukraine. The BME-ENA “Biomedical Engineering Education Tempus Initiative in Eastern Neighbouring Area”, Project Number: 543904-TEMPUS-1-2013-1-GR-TEMPUS-JPCR is a Joint Project within the TEMPUS IV program. This project has been funded with support from the European Commission.Навчальний посібник присвячено розробці методів та засобів для неінвазивного виявлення та дослідження тонких проявів електричної активності серця. Особлива увага приділяється вдосконаленню інформаційного та алгоритмічного забезпечення систем електрокардіографії високого розрізнення для ранньої діагностики електричної нестабільності міокарда, а також для оцінки функціонального стану плоду під час вагітності. Теоретичні основи супроводжуються прикладами реалізації алгоритмів за допомогою системи MATLAB. Навчальний посібник призначений для студентів, аспірантів, а також фахівців у галузі біомедичної електроніки та медичних працівників.The teaching book is devoted to development and research of methods and tools for non-invasive detection of subtle manifistations of heart electrical activity. Particular attention is paid to the improvement of information and algorithmic support of high resolution electrocardiography for early diagnosis of myocardial electrical instability, as well as for the evaluation of the functional state of the fetus during pregnancy examination. The theoretical basis accompanied by the examples of implementation of the discussed algorithms with the help of MATLAB. The teaching book is intended for students, graduate students, as well as specialists in the field of biomedical electronics and medical professionals

Systolic ejection murmurs and the left ventricular outflow tract in boxer dogs

Turbulence of various genesis in the left ventricular outflow tract (LVOT) causes systolic ejection murmurs. The prevalence of murmurs in adult boxer dogs is 50-80%, the majority of which are of low intensity. Some of the murmurs are caused by aortic stenosis (AS), while the origin of the others is unclear. The aim of this thesis was to study the physiology and clinical evaluation of systolic ejection murmurs and their relation to the development of the LVOT in boxers with and without AS. Growing and adult boxer dogs were examined by the standard methods cardiac auscultation, ECG, phonocardiography and echocardiography. Additionally, the complementary methods time-frequency and complexity analyses of heart murmurs and contrast echocardiography were evaluated. Studies on inter-observer variation in cardiac auscultation proved the importance of experience in detection and grading of low intensity ejection murmurs. Excitement of the dogs by exercise or noise stimulation (barking dog and squeaky toy) caused higher murmur grades, longer murmur duration and increased aortic flow velocities. No differences were found between diameters measured at different levels of the LVOT in growing boxers. Contrast echocardiography enhanced Doppler signals, but did not allow evaluation of myocardial blood flow. Using time-frequency analysis, duration of murmur frequency >200 Hz proved useful for differentiation between dogs with mild AS and dogs without. Combining assessment of murmur duration >200 Hz and complexity analysis using the correlation dimension (T2), a sensitivity of 94% and a specificity of 82% for differentiation between dogs with and without AS was achieved. The variability in presence and intensity of low intensity murmurs during growth was high. None of the young dogs developed AS, whereas 3 out of 16 individuals developed mild-moderate aortic insufficiency. Aortic or pulmonic flow velocities did not differ significantly between growing dogs with or without low intensity murmurs. In conclusion, the variability in presence and intensity of low intensity ejection murmurs in boxers is high during growth with no obvious progression. Both in young and adult boxers the murmur grade increased during excitement, which may be due to rapid flow in a comparatively small LVOT that has been suggested for the boxer breed. Experience is important in cardiac auscultation of low intensity murmurs. Therefore, assessment of murmur duration > 200 Hz combined with T2 analysis may be a useful complementary method for diagnosis of cardiovascular function in dogs

Assessment of the dynamics of atrial signals and local atrial period series during atrial fibrillation: effects of isoproterenol administration

BACKGROUND: The autonomic nervous system (ANS) plays an important role in the genesis and maintenance of atrial fibrillation (AF), but quantification of its electrophysiologic effects is extremely complex and difficult. Aim of the study was to evaluate the capability of linear and non-linear indexes to capture the fine changing dynamics of atrial signals and local atrial period (LAP) series during adrenergic activation induced by isoproterenol (a sympathomimetic drug) infusion. METHODS: Nine patients with paroxysmal or persistent AF (aged 60 ± 6) underwent electrophysiological study in which isoproterenol was administered to patients. Atrial electrograms were acquired during i) sinus rhythm (SR); ii) sinus rhythm during isoproterenol (SRISO) administration; iii) atrial fibrillation (AF) and iv) atrial fibrillation during isoproterenol (AFISO) administration. The level of organization between two electrograms was assessed by the synchronization index (S), whereas the degree of recurrence of a pattern in a signal was defined by the regularity index (R). In addition, the level of predictability (LP) and regularity of LAP series were computed. RESULTS: LAP series analysis shows a reduction of both LP and R index during isoproterenol infusion in SR and AF (R(SR )= 0.75 ± 0.07 R(SRISO )= 0.69 ± 0.10, p < 0.0001; R(AF )= 0.31 ± 0.08 R(AFISO )= 0.26 ± 0.09, p < 0.0001; LP(SR )= 99.99 ± 0.001 LP(SRISO )= 99.97 ± 0.03, p < 0.0001; LP(AF )= 69.46 ± 21.55 LP(AFISO )= 55 ± 24.75; p < 0.0001). Electrograms analysis shows R index reductions both in SR (R(SR )= 0.49 ± 0.08 R(SRISO )= 0.46 ± 0.09 p < 0.0001) and in AF (R(AF )= 0.29 ± 0.09 R(AFISO )= 0.28 ± 0.08 n.s.). CONCLUSIONS: The proposed parameters succeeded in discriminating the subtle changes due to isoproterenol infusion during both the rhythms especially when considering LAP series analysis. The reduced value of analyzed parameters after isoproterenol administration could reflect an important pro-arrhythmic influence of adrenergic activation on favoring maintenance of AF

Investigating the protective role of the natural hormone Melatonin, in reducing drug-induced cardiotoxicity in the therapy of chronic diseases

Heart failure (HF) is a highly complex disorder and a major end-point of cardiovascular diseases (CVD). The pathogenesis of HF is mostly unresolved but involves interplay between cardiac structural and electrical remodelling, metabolic alterations, cell death and altered gene expression. Mitochondrial dysfunction and HF are common complications of chronic treatment from diverse groups of drugs, in particular anticancer drugs such as doxorubicin (DOX). Treatment of animals and cardiomyocytes with cardiotoxic chemicals such as β-adrenergic receptor agonists (such as isoproterenol) induces cardiac dysfunction and HF. Previous work done by the group have identified the pineal hormone melatonin was protective against stress-induced cardiac arrhythmias and simulated heart failure in cardiomyocytes in vitro. Melatonin synthesis is also dramatically decreased with age and in patients with CVD. The aim of the present project was to better understand the pathogenesis of druginduced cardiac dysfunction and delineate the role of melatonin in cardioprotection in H9c2, a model rat cell line in vitro. Using the Seahorse XF analyser method, it was demonstrated that commonly used medication for chronic diseases such as amiodarone, amitriptyline, and statins all caused altered mitochondrial dysfunction. In addition, cardiotoxic chemicals (isoproterenol, hydrogen peroxide, DOX) altered oxidative phosphorylation and glycolysis in living cardiomyocyte-derived H9c2 cells; these deleterious metabolic changes were ameliorated by melatonin. Flowcytometry and Alamar Blue staining methods demonstrated that DOX robustly induced apoptosis in H9c2 cells (~30%) which was reversed by melatonin. Doxorubicin-induced stress in H9c2 cells dramatically altered gene expression in several key signalling pathways integral in cardiac function and disease. These included mitochondrial metabolism (UCP2, PPARɣ, Drp1, Mfn1, Parp 1, Parp2, Sirt3 and Cav3), apoptosis (Bcl2 and Bcl-xL), cardiac electrophysiology and arrhythmia (Scn5a, SERCA2a), calcium handling (SERCA2a) and cardiac remodelling (Myh7, ms1). Melatonin pre-treatment attenuated or completely blocked this DOX-induced alteration in gene expression in cardiomyocytes. In conclusion, the present result demonstrated for the first time that melatonin is cardioprotective against drug-induced cardiotoxicity and apoptosis via modifying diverse heart failure-related signalling pathways. This provides novel insight on the possible use of melatonin as an adjunct intervention in several therapies including anti-cancer