Nonlinear physics of electrical wave propagation in the heart: a review

The beating of the heart is a synchronized contraction of muscle cells (myocytes) that are triggered by a periodic sequence of electrical waves (action potentials) originating in the sino-atrial node and propagating over the atria and the ventricles. Cardiac arrhythmias like atrial and ventricular fibrillation (AF,VF) or ventricular tachycardia (VT) are caused by disruptions and instabilities of these electrical excitations, that lead to the emergence of rotating waves (VT) and turbulent wave patterns (AF,VF). Numerous simulation and experimental studies during the last 20 years have addressed these topics. In this review we focus on the nonlinear dynamics of wave propagation in the heart with an emphasis on the theory of pulses, spirals and scroll waves and their instabilities in excitable media and their application to cardiac modeling. After an introduction into electrophysiological models for action potential propagation, the modeling and analysis of spatiotemporal alternans, spiral and scroll meandering, spiral breakup and scroll wave instabilities like negative line tension and sproing are reviewed in depth and discussed with emphasis on their impact in cardiac arrhythmias.Peer ReviewedPreprin

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 171

This bibliography lists 186 reports, articles, and other documents introduced into the NASA scientific and technical information system in August 1977

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 159

This bibliography lists 257 reports, articles, and other documents introduced into the NASA scientific and technical information system in September 1976

Part II

The molecular mechanisms of the pharmacological action of SS-68 were chosen as the focus for this study. From the point of view of molecular pharmacology, SS-68 can be attributed to an antiarrhythmic drug with a mixed type of actio

Aerospace Medicine and Biology: A continuing supplement 180, May 1978

This special bibliography lists 201 reports, articles, and other documents introduced into the NASA scientific and technical information system in April 1978

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

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 130, July 1974

This special bibliography lists 291 reports, articles, and other documents introduced into the NASA scientific and technical information system in June 1974

Modified mass-spring system for physically based deformation modeling

Mass-spring systems are considered the simplest and most intuitive of all deformable models. They are computationally efficient, and can handle large deformations with ease. But they suffer several intrinsic limitations. In this book a modified mass-spring system for physically based deformation modeling that addresses the limitations and solves them elegantly is presented. Several implementations in modeling breast mechanics, heart mechanics and for elastic images registration are presented