multi-system-monitoring-for-identification-seizures-arrhythmias-apnea

Multi-system Monitoring for Identification of Seizures, Arrhythmias and Apnea in Conscious Restrained Rabbits

Patients with ion channelopathies are at a high risk of developing seizures and fatal cardiac arrhythmias. There is a higher prevalence of heart disease ...

surgical-implant-procedure-wiring-configuration-for-continuous-long

Surgical Implant Procedure and Wiring Configuration for Continuous Long-Term EEG/ECG Monitoring in Rabbits

A multi-system approach that includes the continuous collection of electroencephalogram (EEG) and electrocardiogram (ECG) recordings facilitates a ...

Upstate Medical University

SUNY Upstate Medical University

Ventricular fibrillation (VF) is the leading cause of sudden cardiac death. This brief review addresses issues relevant to the dynamics of the rotors responsible for functional reentry and VF. It also makes an attempt to summarize present-day knowledge of the manner in which the dynamic interplay between inward and outward transmembrane currents and the heterogeneous cardiac structure establish a substrate for the initiation and maintenance of rotors and VF. The fragmentary nature of our current understanding of ionic VF mechanisms does not even allow an approach toward a "Theory of VF". Yet some hope is provided by recently obtained insight into the roles played in VF by some of the sarcolemmal ion channels that control the excitation-recovery process. For example, strong evidence supports the idea that the interplay between the rapid-inward sodium current and the inward-rectifier potassium current controls rotor formation, as well as rotor stability and frequency. Solid evidence also exists for an involvement of L-type calcium current in the control of rotor frequency and in determining VF-to-ventricular tachycardia conversion. Less clear, however, is whether or not time dependent outward currents through voltage-gated potassium channels affect the fibrillatory process. Hopefully, taking advantage of currently available approaches of structural, molecular and cellular biology, together with computational and imaging techniques, will afford us the opportunity to further advance knowledge on VF mechanisms.

Ventricular fibrillation: dynamics and ion channel determinants.

&#x5FC3;&#x529B;&#x8870;&#x7AED; &#xFF08;HF&#xFF09; &#x901A;&#x5E38;&#x5BFC;&#x81F4;&#x5FC3;&#x623F;&#x7EA4;&#x98A4; (AF) &#x548C;&#x7EA4;&#x7EF4;&#x5316;&#xFF0C;&#x4F46;&#x5206;&#x5E03;&#x7684;&#x7EA4;&#x7EF4;&#x5316;&#x5982;&#x4F55;&#x5F71;&#x54CD; AF &#x52A8;&#x529B;&#x5B66;&#x4E0D;&#x7814;&#x7A76;&#x3002;HF &#x662F;&#x7F8A;&#x81F4;&#x5FC3;&#x5BA4;&#x8D77;&#x640F; (220 bpm&#xFF0C;6 &#x5230; 7 &#x5468;)&#x3002;&#x540E;&#x5DE6;&#x5FC3;&#x623F; (PLA) &#x5185;&#x819C;&#x7684;&#x5149;&#x5B66;&#x6620;&#x5C04; &#xFF08;Di-4-ANEPPS&#xFF0C;300 &#x5E27;/&#x79D2;&#xFF09; &#x6267;&#x884C;&#x671F;&#x95F4;&#x6301;&#x7EED; AF (&#x7A81;&#x53D1;&#x8D77;&#x640F;&#xFF09; &#x5728;&#x704C;&#x6CE8;&#x65F6; HF (n = 7&#xFF0C;4 &#x5FAE;&#x6469;&#x5C14;/&#x5347;&#x4E59;&#x9170;&#x80C6;&#x78B1; &#xFF1B; n = 3&#xFF0C;&#x6CA1;&#x6709;&#x4E59;&#x9170;&#x80C6;&#x78B1;&#xFF09; &#x548C;&#x63A7;&#x5236; &#xFF08;n = 6) &#x5FC3;&#x3002;&#x4E2D;&#x56FD;&#x4EBA;&#x6C11;&#x89E3;&#x653E;&#x519B;&#x7A81;&#x7834;&#x4E86;&#x8FD9;&#x4E24;&#x4E2A;&#x7EC4;&#x7684;&#x6700;&#x9891;&#x7E41;&#x6FC0;&#x6D3B;&#x6A21;&#x5F0F; (+ /-4.6 &#x548C; + /-2.7%&#xFF0C;&#x9AD8;&#x9891;&#x548C;&#x63A7;&#x5236;&#xFF0C;90.2 720 &#x5206;&#x522B;)&#x3002;&#x7136;&#x800C;&#xFF0C;&#x4E0E;&#x63A7;&#x4EF6;&#x4E0D;&#x540C;&#xFF0C;&#x9AD8;&#x9891;&#x7A81;&#x7834;&#x4F18;&#x5148;&#x53D1;&#x751F;&#x5728;&#x5851;&#x6599;&#x5916;&#x56F4;&#x9644;&#x8FD1;&#x80BA;&#x9759;&#x8109;&#x7AA6;&#x53E3;&#xFF0C;&#x548C;&#x4ED6;&#x4EEC;&#x62CD;&#x7684;&#x53D8;&#x5F02;&#x6027;&#x662F;&#x5927;&#x4E8E;&#x63A7;&#x5236; (+ /-1.47+/-0.07 &#x53D8;&#x5316;&#x4E0E; 0.14 1.93 / [&#x8282;&#x62CD;/&#x79D2;]&#xFF0C;&#x5206;&#x522B; P &lt; 0.05&#xFF09;&#x3002;&#x7EC4;&#x7EC7;&#x5B66;&#x5206;&#x6790; &#xFF08;picrosirius &#x7EA2;&#x8272;&#xFF09;&#x3001; &#x5F25;&#x6F2B;&#x6027;&#x7EA4;&#x7EF4;&#x5316;&#x9886;&#x57DF;&#x662F; HF (23.4 + /-0.4%) &#x5927;&#x4E8E;&#x63A7;&#x5236; (14.1 + /-0.6%&#xFF1B;P &lt; 0.001&#xFF0C;n = 4&#xFF09;&#x3002;&#x6B64;&#x5916;&#x7684;&#x6570;&#x91CF;&#x548C;&#x5927;&#x5C0F;&#x7684;&#x7EA4;&#x7EF4;&#x4FEE;&#x8865;&#x7A0B;&#x5E8F;&#x88AB;&#x5927;&#x548C;&#x5B83;&#x4EEC;&#x7684;&#x4F4D;&#x7F6E;&#x662F;&#x5728; HF &#x6BD4;&#x63A7;&#x5236;&#x66F4;&#x591A;&#x7684;&#x5916;&#x56F4;&#x3002;&#x7528; 2 &#x7EF4;&#x4EBA;&#x7C7B;&#x5FC3;&#x623F;&#x6A21;&#x578B;&#x7ED3;&#x6784;&#x548C;&#x79BB;&#x5B50;&#x91CD;&#x6784;&#x4E0E; HF &#x7684;&#x8BA1;&#x7B97;&#x673A;&#x6A21;&#x62DF;&#x8868;&#x660E; AF &#x6FC0;&#x6D3B;&#x9891;&#x7387;&#x548C;&#x52A8;&#x6001;&#x53D8;&#x5316;&#x90FD;&#x7531;&#x6CE2;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x7684;&#x7535;&#x6C14;&#x4E0E;&#x809D;&#x7EA4;&#x7EF4;&#x5316;&#x7684;&#x5404;&#x79CD;&#x5927;&#x5C0F;&#x548C;&#x4E2A;&#x522B;&#x80BA;&#x9759;&#x8109;&#x7AA6;&#x53E3;&#x7684;&#x4FEE;&#x8865;&#x7A0B;&#x5E8F;&#x7684;&#x7FA4;&#x96C6;&#x3002;&#x5728;&#x6CA1;&#x6709;&#x5FC3;&#x7684; AF&#xFF0C;&#x5F02;&#x6784;&#x7A7A;&#x95F4;&#x5206;&#x5E03;&#x7684;&#x7EA4;&#x7EF4;&#x5728;&#x4E2D;&#x56FD;&#x4EBA;&#x6C11;&#x89E3;&#x653E;&#x519B; AF &#x52A8;&#x529B;&#x5B66;&#x548C;&#x5206;&#x998F;&#x7BA1;&#x8F96;&#x3002;

&#x7A7A;&#x95F4;&#x5206;&#x5E03;&#x7684;&#x7EA4;&#x7EF4;&#x5316;&#x671F;&#x95F4;&#x5FC3;&#x8870;&#x63A7;&#x5236;&#x540E;&#x5DE6;&#x5FC3;&#x623F;&#x98A4;&#x52A8;&#x6CE2;&#x52A8;&#x529B;&#x5B66;&#x3002;

Heart failure (HF) commonly results in atrial fibrillation (AF) and fibrosis, but how the distribution of fibrosis impacts AF dynamics has not been studied. HF was induced in sheep by ventricular tachypacing (220 bpm, 6 to 7 weeks). Optical mapping (Di-4-ANEPPS, 300 frames/sec) of the posterior left atrial (PLA) endocardium was performed during sustained AF (burst pacing) in Langendorff-perfused HF (n=7, 4 micromol/L acetylcholine; n=3, no acetylcholine) and control (n=6) hearts. PLA breakthroughs were the most frequent activation pattern in both groups (72.0+/-4.6 and 90.2+/-2.7%, HF and control, respectively). However, unlike control, HF breakthroughs preferentially occurred at the PLAs periphery near the pulmonary vein ostia, and their beat-to-beat variability was greater than control (1.93+/-0.14 versus 1.47+/-0.07 changes/[beats/sec], respectively, P<0.05). On histological analysis (picrosirius red), the area of diffuse fibrosis was larger in HF (23.4+/-0.4%) than control (14.1+/-0.6%; P<0.001, n=4). Also the number and size of fibrous patches were significantly larger and their location was more peripheral in HF than control. Computer simulations using 2-dimensional human atrial models with structural and ionic remodeling as in HF demonstrated that changes in AF activation frequency and dynamics were controlled by the interaction of electrical waves with clusters of fibrotic patches of various sizes and individual pulmonary vein ostia. During AF in failing hearts, heterogeneous spatial distribution of fibrosis at the PLA governs AF dynamics and fractionation.

Spatial distribution of fibrosis governs fibrillation wave dynamics in the posterior left atrium during heart failure.

Insuffisance cardiaque (IC) entra&#xEE;ne g&#xE9;n&#xE9;ralement la fibrillation auriculaire (FA) et la fibrose, mais comment la distribution de la fibrose dynamique impacts AF n&#x26;#39;a pas &#xE9;t&#xE9; &#xE9;tudi&#xE9;e. HF a &#xE9;t&#xE9; induite chez le mouton par tachypacing ventriculaire (220 bpm, 6 &#xE0; 7 semaines). Cartographie optique (Di-4-ANEPPS, 300 images par seconde) de la partie post&#xE9;rieure de l&#x26;#39;oreillette gauche (PLA) endocarde a &#xE9;t&#xE9; effectu&#xE9;e pendant soutenue AF (stimulation de salve) dans Langendorff perfus&#xE9; HF (n = 7, 4 micromoles / L ac&#xE9;tylcholine; n = 3, n &#xB0; ac&#xE9;tylcholine) et de contr&#xF4;le (n = 6) coeurs. Perc&#xE9;es de l&#x26;#39;APL ont &#xE9;t&#xE9; le motif d&#x26;#39;activation la plus fr&#xE9;quente dans les deux groupes (72,0 + / -4,6 et 90,2 + / -2,7%, HF et de contr&#xF4;le, respectivement). Cependant, contrairement &#xE0; un contr&#xF4;le, les perc&#xE9;es HF pr&#xE9;f&#xE9;rentiellement produite &#xE0; la p&#xE9;riph&#xE9;rie PLA pr&#xE8;s de la veine pulmonaire ostia, et leur beat-to-beat variabilit&#xE9; &#xE9;tait plus grande que le contr&#xF4;le (1,93 + / -0,14 versus 1,47 + / -0,07 changements / [battements / s] , respectivement, P &#x26;lt;0,05). Lors de l&#x26;#39;analyse histologique (picrosirius rouge), le domaine de la fibrose diffuse &#xE9;tait plus grande en HF (23,4 + / -0,4%) que le contr&#xF4;le (14,1 + / -0,6%, p &#x26;lt;0,001, n = 4). De plus, le nombre et la taille des parcelles fibreuses &#xE9;taient significativement plus grands et leur emplacement &#xE9;tait plus p&#xE9;riph&#xE9;rique en HF de contr&#xF4;le. Des simulations sur ordinateur en utilisant 2-dimensionnelles des mod&#xE8;les humains auriculaire avec une r&#xE9;organisation structurelle et ionique en HF d&#xE9;montr&#xE9; que les changements dans la fr&#xE9;quence d&#x26;#39;activation AF et la dynamique ont &#xE9;t&#xE9; contr&#xF4;l&#xE9;es par l&#x26;#39;interaction des ondes &#xE9;lectriques avec des clusters de patchs fibrotiques de diff&#xE9;rentes tailles et individuelle ostia veine pulmonaire. Au cours de la FA dans les coeurs d&#xE9;faillants, h&#xE9;t&#xE9;rog&#xE8;ne de la distribution spatiale de la fibrose &#xE0; la dynamique de PLA r&#xE9;git AF et le fractionnement.

R&#xE9;partition spatiale de la dynamique R&#xE9;git la fibrose vague fibrillation dans l&#x26;#39;Atrium post&#xE9;rieur gauche au cours de l&#x26;#39;insuffisance cardiaque

Herzinsuffizienz (HF) f&uuml;hrt h&auml;ufig zu Vorhofflimmern (AF) und Fibrose, aber wie wirkt sich die Verteilung der Fibrose AF-Dynamik wurde nicht untersucht. HF wurde im Schaf von ventrikul&auml;ren Tachypacing (220 Bpm, 6 bis 7 Wochen) ausgel&ouml;st. Optische Zuordnung (Di-4-ANEPPS, 300 Bilder/Sek) von der hinteren linken Vorhof (PLA) Endokard erfolgte w&auml;hrend der anhaltenden AF (Burst-Stimulation) in Langendorff-perfused HF (n = 7, 4 Mikromol/L Acetylcholin; n = 3, keine Acetylcholin) und Kontrolle (n = 6) Herzen. PLA Durchbr&uuml;che waren die h&auml;ufigsten Aktivierungsmuster in beiden Gruppen (72.0 +/-4.6 und 90.2 +/-2,7 %, HF und Kontrolle, beziehungsweise). Jedoch im Gegensatz-Steuerelement HF Durchbr&uuml;che aufgetreten sind vorzugsweise an der PLAs-Peripherie nahe der Pulmonary Vein-Ostia und ihre Beat-to-Beat-Variabilit&auml;t war gr&ouml;&szlig;er als Steuerelement (1,93 +/-0,14 gegen&uuml;ber 1.47+/-0.07 &Auml;nderungen / [Schl&auml;ge/Sek.], P &lt; 0,05). Histologische Analyse (Picrosirius rot) war das Gebiet des diffuse Fibrose im HF (23,4 +/-0.4 %) h&ouml;her als Steuerelement (14.1 +/-0,6 %; P &lt; 0.001, n = 4). Auch die Anzahl und Gr&ouml;&szlig;e der faserigen Patches waren deutlich gr&ouml;&szlig;er und ihre Lage war entlegeneren in HF als Steuerelement. Verwendung 2-dimensionale menschliche Vorhofflimmern Modelle mit strukturellen und Ionischen Umbau wie in HF Computersimulationen gezeigt, dass Ver&auml;nderungen der AF-Aktivierung-Frequenz und Dynamik durch die Interaktion der elektrischen Wellen mit Clustern fibrotische Patches verschiedener Gr&ouml;&szlig;en und individuelle Pulmonary Vein Ostia gesteuert wurden. W&auml;hrend AF in Ermangelung Herzen regelt die heterogenen r&auml;umliche Verteilung der Fibrose bei der PLA AF-Dynamik und Fraktionierung.

R&auml;umliche Verteilung der Fibrose regelt Kammerflimmern Welle Dynamik in den hinteren linken Vorhof w&auml;hrend der Herzinsuffizienz.

Insufficienza cardiaca (HF) risultati comunemente in fibrillazione atriale (AF) e fibrosi, ma come la distribuzione della fibrosi impatti dinamiche AF non &egrave; stato studiato. HF &egrave; stata indotta in pecore da tachypacing ventricolare (220 bpm, 6-7 settimane). Mappatura ottico (Di-4-ANEPPS, 300 fotogrammi/sec) della posteriore sinistra endocardio atriale di (PLA) &egrave; stata eseguita durante AF sostenuta (stimolazione burst) in HF Langendorff perfusi (n = 7, acetilcolina micromol/L 4; n = 3, no acetilcolina) e controllo (n = 6) cuori. Scoperte PLA sono stati il pattern di attivazione pi&ugrave; frequente in entrambi i gruppi (72,0 + 4,6 e 90,2 + 2,7%, HF e controllo, rispettivamente). Tuttavia, a differenza del controllo, scoperte HF preferenzialmente avvenuto alla periferia di PLAs vicino ostia la vena polmonare, e loro variabilit&agrave; beat-to-beat era maggiore di controllo (1,93 + /-0.14 versus 1.47+/-0.07 modifiche / [battiti/sec], rispettivamente, P &lt; 0,05). Su analisi istologica (picrosirius rosso), l&#39;area di fibrosi diffusa era maggiore in HF (23,4 &plusmn; 0,4%) di controllo (14,1 &plusmn; 0,6%; P &lt; 0,001, n = 4). Anche il numero e le dimensioni delle patch fibrosa erano significativamente pi&ugrave; grandi e loro posizione era pi&ugrave; periferici in HF di controllo. Simulazioni al computer utilizzando modelli atriale umani 2-dimensionale con strutturale e ionici rimodellamento come HF ha dimostrato che le modifiche nella frequenza di attivazione AF e dinamiche erano controllate dall&#39;interazione delle onde elettriche con grappoli di fibrotici chiazze di varie dimensioni e singoli vena polmonare ostia. Durante AF in mancanza di cuori, eterogenea distribuzione spaziale della fibrosi presso il PLA disciplina AF dinamica e frazionamento.

Distribuzione spaziale di fibrosi disciplina dinamica onda fibrillazione nell&#39;atrio sinistro posteriore durante il guasto di cuore.

&#x5FC3;&#x4E0D;&#x5168;&#xFF08;HF&#xFF09;&#x5FC3;&#x623F;&#x7D30;&#x52D5;&#xFF08;AF&#xFF09;&#x3068;&#x7DDA;&#x7DAD;&#x75C7;&#x3067;&#x4E00;&#x822C;&#x7684;&#x306B;&#x305D;&#x306E;&#x7D50;&#x679C;&#x304C;&#x3001;&#x3069;&#x306E;&#x3088;&#x3046;&#x306B;&#x7DDA;&#x7DAD;&#x5316;&#x306E;&#x5F71;&#x97FF;AF&#x30C0;&#x30A4;&#x30CA;&#x30DF;&#x30AF;&#x30B9;&#x306E;&#x5206;&#x5E03;&#x304C;&#x691C;&#x8A0E;&#x3055;&#x308C;&#x3066;&#x3044;&#x306A;&#x3044;&#x3002; HF&#x306F;&#x5FC3;&#x5BA4;tachypacing&#xFF08;220 BPM&#x3001;6&#x304B;&#x3089;7&#x9031;&#xFF09;&#x3067;&#x7F8A;&#x306B;&#x8A98;&#x5C0E;&#x3055;&#x308C;&#x305F;&#x3002;&#x5F8C;&#x90E8;&#x5DE6;&#x5FC3;&#x623F;&#xFF08;PLA&#xFF09;&#x5FC3;&#x5185;&#x819C;&#x306E;&#x5149;&#x5B66;&#x7684;&#x30DE;&#x30C3;&#x30D4;&#x30F3;&#x30B0;&#xFF08;&#x30B8;-4-ANEPPS&#x3001;300&#x30D5;&#x30EC;&#x30FC;&#x30E0;/&#x79D2;&#xFF09;&#x304C;&#x30E9;&#x30F3;&#x30B2;&#x30F3;&#x30C9;&#x30EB;&#x30D5;&#x704C;&#x6D41;HF&#xFF08;n = 7&#x306E;4&#x30DE;&#x30A4;&#x30AF;&#x30ED;&#x30E2;&#x30EB;/ L&#x30A2;&#x30BB;&#x30C1;&#x30EB;&#x30B3;&#x30EA;&#x30F3;&#x3067;&#x6301;&#x7D9A;&#x7684;&#x306A;AF&#xFF08;&#x30D0;&#x30FC;&#x30B9;&#x30C8;&#x30DA;&#x30FC;&#x30B7;&#x30F3;&#x30B0;&#xFF09;&#x306E;&#x9593;&#x306B;&#x884C;&#x308F;&#x308C;&#x305F;&#x3002;N = 3&#x3001;&#x7121;&#x30A2;&#x30BB;&#x30C1;&#x30EB;&#x30B3;&#x30EA;&#x30F3;&#xFF09;&#x3068;&#x30B3;&#x30F3;&#x30C8;&#x30ED;&#x30FC;&#x30EB;&#xFF08;n = 6&#xFF09;&#x306E;&#x5FC3;&#x3002; PLA&#x306E;&#x30D6;&#x30EC;&#x30FC;&#x30AF;&#x30B9;&#x30EB;&#x30FC;&#x306F;&#x4E21;&#x7FA4;&#x3067;&#x6700;&#x3082;&#x983B;&#x7E41;&#x306B;&#x6D3B;&#x6027;&#x5316;&#x30D1;&#x30BF;&#x30FC;&#x30F3;&#xFF08;HF&#x200B;&#x200B;&#x304A;&#x3088;&#x3073;&#x5236;&#x5FA1;&#x306F;&#x3001;&#x305D;&#x308C;&#x305E;&#x308C;72.0 + / -4.6&#x304A;&#x3088;&#x3073;90.2 + / -2.7&#xFF05;&#xFF09;&#x3067;&#x3042;&#x3063;&#x305F;&#x3002;&#x3057;&#x304B;&#x3057;&#x3001;&#x30B3;&#x30F3;&#x30C8;&#x30ED;&#x30FC;&#x30EB;&#x3068;&#x306F;&#x7570;&#x306A;&#x308A;&#x3001;HF&#x306E;&#x30D6;&#x30EC;&#x30FC;&#x30AF;&#x30B9;&#x30EB;&#x30FC;&#x306F;&#x3001;&#x512A;&#x5148;&#x7684;&#x306B;&#x80BA;&#x9759;&#x8108;&#x5165;&#x53E3;&#x90E8;&#x306E;&#x8FD1;&#x304F;&#x306B;PLA&#x3067;&#x5468;&#x8FBA;&#x90E8;&#x3067;&#x767A;&#x751F;&#x3057;&#x3001;&#x305D;&#x306E;&#x30D3;&#x30FC;&#x30C8;&#x306B;&#x30D3;&#x30FC;&#x30C8;&#x5909;&#x52D5;&#x306F;&#x30B3;&#x30F3;&#x30C8;&#x30ED;&#x30FC;&#x30EB;&#xFF08;1.93 + / -0.14&#x5BFE;1.47 + / -0.07&#x5909;&#x66F4;/ [&#x62CD;/&#x79D2;]&#x3088;&#x308A;&#x3082;&#x5927;&#x304D;&#x304B;&#x3063;&#x305F;&#x305D;&#x308C;&#x305E;&#x308C;&#x3001;P &#x26;lt;0.05&#xFF09;&#x3002;&#x7D44;&#x7E54;&#x5B66;&#x7684;&#x5206;&#x6790;&#xFF08;picrosirius&#x8D64;&#xFF09;&#x3067;&#x3001;&#x3073;&#x307E;&#x3093;&#x6027;&#x7DDA;&#x7DAD;&#x75C7;&#x306E;&#x9818;&#x57DF;&#x306B;&#x306F;&#x3001;&#x30B3;&#x30F3;&#x30C8;&#x30ED;&#x30FC;&#x30EB;&#xFF08;P &#x26;lt;0.001&#x3001;n = 4&#x3067;14.1 + / -0.6&#xFF05;&#xFF09;&#x3088;&#x308A;&#x3082;HF&#xFF08;23.4 + / -0.4&#xFF05;&#xFF09;&#x3067;&#x5927;&#x304D;&#x304B;&#x3063;&#x305F;&#x3002;&#x307E;&#x305F;&#x3001;&#x7E4A;&#x7DAD;&#x72B6;&#x306E;&#x30D1;&#x30C3;&#x30C1;&#x306E;&#x6570;&#x3068;&#x30B5;&#x30A4;&#x30BA;&#x304C;&#x6709;&#x610F;&#x306B;&#x5927;&#x304D;&#x304B;&#x3063;&#x305F;&#x3068;&#x305D;&#x306E;&#x5834;&#x6240;&#x306F;&#x30B3;&#x30F3;&#x30C8;&#x30ED;&#x30FC;&#x30EB;&#x306B;&#x6BD4;&#x3079;&#x3066;HF&#x3088;&#x308A;&#x5468;&#x8FBA;&#x3067;&#x3042;&#x3063;&#x305F;&#x3002; HF&#x306E;&#x3088;&#x3046;&#x306A;&#x69CB;&#x9020;&#x3068;&#x30A4;&#x30AA;&#x30F3;&#x306E;&#x30E2;&#x30C7;&#x30EA;&#x30F3;&#x30B0;&#x3068;2&#x6B21;&#x5143;&#x306E;&#x30D2;&#x30C8;&#x5FC3;&#x623F;&#x30E2;&#x30C7;&#x30EB;&#x3092;&#x7528;&#x3044;&#x305F;&#x30B3;&#x30F3;&#x30D4;&#x30E5;&#x30FC;&#x30BF;&#x30B7;&#x30DF;&#x30E5;&#x30EC;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x3067;&#x306F;&#x3001;AF&#x306E;&#x6D3B;&#x6027;&#x5316;&#x5468;&#x6CE2;&#x6570;&#x3068;&#x30C0;&#x30A4;&#x30CA;&#x30DF;&#x30AF;&#x30B9;&#x306E;&#x5909;&#x5316;&#x306F;&#x69D8;&#x3005;&#x306A;&#x30B5;&#x30A4;&#x30BA;&#x3068;&#x500B;&#x3005;&#x306E;&#x80BA;&#x9759;&#x8108;&#x5165;&#x53E3;&#x90E8;&#x306E;&#x7DDA;&#x7DAD;&#x5316;&#x30D1;&#x30C3;&#x30C1;&#x306E;&#x30AF;&#x30E9;&#x30B9;&#x30BF;&#x30FC;&#x3068;&#x306E;&#x96FB;&#x6C17;&#x7684;&#x306A;&#x6CE2;&#x306E;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x306B;&#x3088;&#x3063;&#x3066;&#x5236;&#x5FA1;&#x3055;&#x308C;&#x305F;&#x3053;&#x3068;&#x3092;&#x660E;&#x3089;&#x304B;&#x306B;&#x3057;&#x305F;&#x3002; AF&#x6642;&#x306E;&#x5FC3;&#x306F;&#x3001;PLA&#x3092;&#x652F;&#x914D;AF&#x30C0;&#x30A4;&#x30CA;&#x30DF;&#x30AF;&#x30B9;&#x3068;&#x5206;&#x5225;&#x306B;&#x304A;&#x3051;&#x308B;&#x7DDA;&#x7DAD;&#x75C7;&#x306E;&#x7570;&#x7A2E;&#x306E;&#x7A7A;&#x9593;&#x5206;&#x5E03;&#x3092;&#x5931;&#x6557;&#x30A4;&#x30F3;&#x30C1;

&#x5FC3;&#x4E0D;&#x5168;&#x6642;&#x306B;&#x5F8C;&#x65B9;&#x5DE6;&#x5FC3;&#x623F;&#x306E;&#x7DDA;&#x7DAD;&#x3092;&#x652F;&#x914D;&#x3059;&#x308B;&#x52D5;&#x6CE2;&#x30C0;&#x30A4;&#x30CA;&#x30DF;&#x30AF;&#x30B9;&#x306E;&#x7A7A;&#x9593;&#x5206;&#x5E03;

&#xC2EC;&#xC7A5; &#xB9C8;&#xBE44; (HF) &#xC2EC; &#xBC29; &#xC138; &#xB3D9; (AF)&#xACFC; &#xC12C;&#xC720; &#xC99D;, &#xC77C;&#xBC18;&#xC801;&#xC73C;&#xB85C; &#xBC1C;&#xC0DD; &#xD558;&#xC9C0;&#xB9CC; &#xC12C;&#xC720; &#xC99D; &#xBD84;&#xD3EC; AF &#xC5ED;&#xD559;&#xC5D0; &#xBBF8;&#xCE58;&#xB294; &#xC601;&#xD5A5; &#xC5F0;&#xAD6C; &#xB418;&#xC9C0; &#xC54A;&#xC558;&#xC2B5;&#xB2C8;&#xB2E4;. HF&#xB294; &#xC591; &#xC2EC; &#xC2E4; tachypacing (220 bpm, 6 ~ 7 &#xC8FC;)&#xC5D0; &#xC758;&#xD574; &#xC720;&#xB3C4; &#xB418;&#xC5C8;&#xB2E4;. &#xAD11;&#xD559; &#xB9E4;&#xD551; (&#xB514;-4-ANEPPS, 300 &#xD504;&#xB808;&#xC784;/&#xCD08;)&#xC758; &#xD6C4;&#xBD80; &#xC67C;&#xCABD;&#xB41C; &#xC2EC; &#xBC29; (PLA) endocardium Langendorff &#xB07C;&#xC5B9;&#xB294;&#xB2E4; HF&#xC758; &#xC9C0;&#xC18D;&#xC801;&#xC778;&#xB41C; AF (&#xD30C;&#xC5F4; &#xC131;) &#xD558;&#xB294; &#xB3D9;&#xC548; &#xC218;&#xD589;&#xD55C; (n = 7, micromol/4l &#xC544; &#xC138; &#xD2F8; &#xCF5C;&#xB9B0;, n = 3, &#xC544;&#xB2C8; &#xC544; &#xC138; &#xD2F8; &#xCF5C;&#xB9B0;) &#xBC0F; &#xC81C;&#xC5B4; (n = 6) &#xB9C8;&#xC74C;. PLA &#xD68D;&#xAE30;&#xC801;&#xC778; &#xD588;&#xB2E4; &#xB450; &#xADF8;&#xB8F9;&#xC5D0;&#xC11C; &#xAC00;&#xC7A5; &#xC790;&#xC8FC; &#xD65C;&#xC131;&#xD654; &#xD328;&#xD134; (+ 4.6 &#xBC0F; &plusmn; 2.7%, HF &#xBC0F; &#xC81C;&#xC5B4;, 90.2 72.0 &#xAC01;&#xAC01;). &#xADF8;&#xB7EC;&#xB098; &#xCEE8;&#xD2B8;&#xB864;&#xACFC; &#xB2EC;&#xB9AC; HF &#xD68D;&#xAE30;&#xC801;&#xC778; &#xC6B0;&#xC120;&#xC801;&#xC73C;&#xB85C; &#xD3D0; &#xC815; &#xB9E5; ostia &#xADFC;&#xCC98; PLAs &#xC8FC;&#xBCC0;&#xC5D0;&#xC11C; &#xBC1C;&#xC0DD; &#xD558; &#xACE0; &#xADF8;&#xB4E4;&#xC758; &#xBE44;&#xD2B8; &#xB300; &#xBE44;&#xD2B8; &#xBCC0;&#xD654;&#xB294; &#xCEE8;&#xD2B8;&#xB864; &#xBCF4;&#xB2E4; &#xD070; (1.47+/-0.07 &#xBCC0;&#xACBD; &#xB300; 0.14 &plusmn; 1.93 / [&#xBE44;&#xD2B8;/&#xCD08;], &#xAC01;&#xAC01; P &lt; 0.05). &#xC870;&#xC9C1;&#xD559; &#xBD84;&#xC11D; (picrosirius &#xB808;&#xB4DC;)&#xC5D0; &#xD655;&#xC0B0; &#xC12C;&#xC720; &#xC99D;&#xC758; &#xC601;&#xC5ED; &#xC81C;&#xC5B4; (14.1 &plusmn; 0.6%; HF (23.4 &plusmn; 0.4%)&#xC5D0; &#xCD08;&#xACFC; &#xD558;&#xB294; P &lt; 0.001, n = 4). &#xB610;&#xD55C; &#xC218;&#xC640; &#xC12C;&#xC720; &#xD328;&#xCE58;&#xC758; &#xD06C;&#xAE30;&#xB97C; &#xC0C1;&#xB2F9;&#xD788; &#xD070; &#xD588;&#xB2E4; &#xADF8;&#xB9AC;&#xACE0; &#xADF8;&#xB4E4;&#xC758; &#xC704;&#xCE58;&#xB294; &#xCEE8;&#xD2B8;&#xB864; &#xBCF4;&#xB2E4;&#xB294; HF&#xC5D0;&#xC11C; &#xC8FC;&#xBCC0;. HF&#xB85C; &#xAC1C;&#xC7A5; &#xD558;&#xB294; &#xAD6C;&#xC870;&#xC640; &#xC774;&#xC628;&#xC73C;&#xB85C; 2 &#xCC28;&#xC6D0; &#xC778;&#xAC04;&#xC758; &#xC2EC; &#xBC29; &#xBAA8;&#xB378;&#xC744; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xCEF4;&#xD4E8;&#xD130; &#xC2DC;&#xBBAC;&#xB808;&#xC774;&#xC158; &#xC2DC;&#xC5F0; &#xC5B4; &#xC815;&#xD488; &#xC778;&#xC99D; &#xBE48;&#xB3C4; &#xC5ED;&#xD559;&#xC758; &#xBCC0;&#xD654; &#xB2E4;&#xC591; &#xD55C; &#xD06C;&#xAE30;&#xC640; &#xAC1C;&#xBCC4; &#xD3D0; &#xC815; &#xB9E5; ostia fibrotic &#xD328;&#xCE58; &#xD074;&#xB7EC;&#xC2A4;&#xD130;&#xC640; &#xC804;&#xAE30; &#xD30C;&#xB3C4;&#xC758; &#xC791;&#xC6A9;&#xC5D0; &#xC758;&#xD574; &#xD1B5;&#xC81C; &#xD588;&#xB2E4;. &#xC2E4;&#xD328; &#xD558;&#xB294; &#xB9C8;&#xC74C;&#xC5D0; &#xC5B4;, &#xD558;&#xB294; &#xB3D9;&#xC548; PLA&#xC5D0; &#xC12C;&#xC720; &#xC99D;&#xC758; &#xC774;&#xAE30;&#xC885; &#xACF5;&#xAC04; &#xBD84;&#xD3EC; &#xC81C;&#xC5B4; AF &#xC5ED;&#xD559;&#xACFC; &#xBD84;&#xB958;.

&#xC12C;&#xC720; &#xC99D;&#xC758; &#xACF5;&#xAC04; &#xBD84;&#xD3EC; &#xC2EC;&#xC7A5; &#xB9C8;&#xBE44; &#xC911; &#xD6C4;&#xBD80; &#xC67C;&#xCABD;&#xB41C; &#xC544; &#xD2B8;&#xB9AC; &#xC6C0;&#xC758; &#xB3D9; &#xD30C;&#xB3D9; &#xC5ED;&#xD559;&#xC744; &#xC81C;&#xC5B4;&#xD569;&#xB2C8;&#xB2E4;.

La insuficiencia cardiaca (IC) suele dar lugar a la fibrilaci&#xF3;n auricular (FA) y la fibrosis, pero &#xBF;c&#xF3;mo la distribuci&#xF3;n de la fibrosis impactos din&#xE1;mica de AF no se ha estudiado. HF fue inducida en ovejas por tachypacing ventricular (220 pulsaciones por minuto, de 6 a 7 semanas). Mapeo &#xF3;ptico (Di-4-ANEPPS, a 300 fotogramas por segundo) de la parte posterior de la aur&#xED;cula izquierda (EPL) de endocardio se realiz&#xF3; durante la FA sostenida (sobreestimulaci&#xF3;n) en Langendorff perfundidos IC (n = 7, 4 micromol / L acetilcolina, n = 3, sin la acetilcolina) y control (n = 6) corazones. Avances del EPL eran el patr&#xF3;n de activaci&#xF3;n m&#xE1;s frecuente en ambos grupos (72,0 + / -4,6 y 90,2 + / -2,7%, HF y control, respectivamente). Sin embargo, a diferencia de control, los avances HF preferentemente se produjo en la periferia, cerca de la ostia PLA vena pulmonar, y su latido a latido la variabilidad fue mayor que el control (1,93 + / -0,14 frente a 1,47 + / -0,07 cambios / [latidos por segundo] , respectivamente, P &#x26;lt;0,05). El an&#xE1;lisis histol&#xF3;gico (picrosirio rojo), el &#xE1;rea de fibrosis difusa fue mayor en la IC (23,4 + / -0,4%) que el control (14,1 + / -0,6%, p &#x26;lt;0,001, n = 4). Asimismo, el n&#xFA;mero y tama&#xF1;o de los parches fibrosos fueron significativamente m&#xE1;s grande y su ubicaci&#xF3;n era m&#xE1;s perif&#xE9;rica en la IC que el control. Las simulaciones por ordenador utilizando dos modelos tridimensionales auriculares humanos con la remodelaci&#xF3;n estructural y i&#xF3;nico como en la insuficiencia cardiaca ha demostrado que los cambios en la frecuencia de activaci&#xF3;n AF y la din&#xE1;mica fueron controladas por la interacci&#xF3;n de las ondas el&#xE9;ctricas con grupos de parches de fibrosis de diferentes tama&#xF1;os y ostia persona vena pulmonar. Durante la FA en los corazones, no de distribuci&#xF3;n espacial heterog&#xE9;nea de la fibrosis en la din&#xE1;mica de PLA administra la AF y el fraccionamiento.

Distribuci&#xF3;n espacial de la din&#xE1;mica de las olas fibrosis Rige fibrilaci&#xF3;n en el atrio posterior izquierdo durante la insuficiencia card&#xED;aca

&#x5FEB;&#x901F;&#x5EF6;&#x8FDF;&#x7684;&#x6574;&#x6D41;&#x94BE;&#x7535;&#x6D41;&#xFF0C;I(Kr)&#xFF0C;&#x5176;&#x4E2D;&#x6D41;&#x7ECF;&#x4EBA;&#x7C7B;&#x919A;-&#x4E00;-go go-&#x6709;&#x5173; (hERG&#xFF09; &#x901A;&#x9053;&#xFF0C;&#x662F;&#x5F62;&#x72B6;&#x7684;&#x4E00;&#x4E2A;&#x4E3B;&#x8981;&#x51B3;&#x5B9A;&#x56E0;&#x7D20;&#x548C;&#x4EBA;&#x7C7B;&#x7684;&#x5FC3;&#x810F;&#x52A8;&#x4F5C;&#x7535;&#x4F4D; (APD) &#x7684;&#x6301;&#x7EED;&#x65F6;&#x95F4;&#x3002;&#x7136;&#x800C;&#xFF0C;&#x662F;&#x672A;&#x77E5;&#x662F;&#x5426;&#x65F6;&#x95F4;&#x4F9D;&#x8D56;&#x6027;&#x7684; I(Kr) &#x53EF;&#x4EE5;&#x63A7;&#x5236; APD&#x3001; &#x4F20;&#x5BFC;&#x901F;&#x5EA6; (CV) &#x548C;&#x6781;&#x9AD8;&#x7684;&#x6FC0;&#x6D3B;&#x9891;&#x7387;&#x6709;&#x5173;&#x5FC3;&#x810F;&#x518D;&#x5165;&#x548C;&#x98A4;&#x52A8;&#x7684;&#x6CE2;&#x957F; &#xFF08;WL&#xFF09;&#x3002;

&#x5728;&#x786E;&#x5B9A;&#x9891;&#x7387;&#x5728;&#x65B0;&#x751F;&#x5927;&#x9F20;&#x5FC3;&#x5BA4;&#x808C;&#x7EC6;&#x80DE;&#x5355;&#x5C42;&#x6298;&#x8FD4; HERG &#x53D1;&#x6325;&#x4E3B;&#x8981;&#x4F5C;&#x7528;&#x3002;

the rapid delayed rectifier potassium current, I(Kr), which flows through the human ether-a-go-go-related (hERG) channel, is a major determinant of the shape and duration of the human cardiac action potential (APD). However, it is unknown whether the time dependency of I(Kr) enables it to control APD, conduction velocity (CV), and wavelength (WL) at the exceedingly high activation frequencies that are relevant to cardiac reentry and fibrillation.

A major role for HERG in determining frequency of reentry in neonatal rat ventricular myocyte monolayer.

le potassium redresseur rapide retard actuel, je (Kr), qui s&#x26;#39;&#xE9;coule &#xE0; travers l&#x26;#39;&#xE9;ther-a-go-go humaines qui en d&#xE9;coulent (hERG) de canal, est un d&#xE9;terminant majeur de la forme et la dur&#xE9;e du potentiel d&#x26;#39;action cardiaque humaine (APD). Toutefois, on ignore si la d&#xE9;pendance temporelle de I (Kr) lui permet de contr&#xF4;ler la DGPA, la vitesse de conduction (CV), et longueur d&#x26;#39;onde (WL) aux fr&#xE9;quences d&#x26;#39;activation extr&#xEA;mement &#xE9;lev&#xE9;es qui sont pertinents pour la rentr&#xE9;e cardiaque et la fibrillation.

Un r&#xF4;le majeur pour d&#xE9;terminer la fr&#xE9;quence HERG de rentr&#xE9;e en monocouche Rat des myocytes n&#xE9;onatals ventriculaire

schnelle verz&ouml;gerten Gleichrichter ist Kalium, I(Kr), der durch den menschlichen &Auml;ther-a-Go-Go-bezogenen (hERG)-Kanal flie&szlig;t, ein wichtiger Faktor der Form und Dauer der das menschliche Herz Aktionspotential (APD). Es ist jedoch unbekannt, ob der Zeitabh&auml;ngigkeit des I(Kr) erm&ouml;glicht es Steuern APD, Leitgeschwindigkeit (CV) und Wellenl&auml;nge (WL) bei den &uuml;beraus hohe Aktivierung-Frequenzen, die f&uuml;r kardiale Reentranz und Kammerflimmern sind.

Eine wichtige Rolle bei der Bestimmung der H&auml;ufigkeit des Wiedereintritts in neonatalen Ratte ventrikul&auml;re Muskelfaser Monolage f&uuml;r HERG.

la corrente di potassio rapida ritardato raddrizzatore, I(Kr), che scorre attraverso il canale di human ether-a-go-go legate (hERG), &egrave; un determinante della forma e della durata del potenziale d&#39;azione cardiaco umano (APD). Tuttavia, non si sa se la dipendenza del tempo di I(Kr) consente al controllo APD, velocit&agrave; di conduzione (CV) e la lunghezza d&#39;onda (WL) alle frequenze estremamente elevata attivazione che sono rilevanti per la fibrillazione e rientro cardiaco.

Un ruolo importante per HERG nel determinare la frequenza del rientro in monostrato ventricolare del miocita neonatali del ratto.

&#x4EBA;&#x9593;&#x306E;&#x30A8;&#x30FC;&#x30C6;&#x30EB;-GO-GO-&#x95A2;&#x9023;&#xFF08;&#x306E;hERG&#xFF09;&#x306F;&#x3001;&#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x306B;&#x6D41;&#x308C;&#x308B;&#x96FB;&#x6D41;&#x306E;&#x6025;&#x901F;&#x306A;&#x9045;&#x5EF6;&#x6574;&#x6D41;&#x30AB;&#x30EA;&#x30A6;&#x30E0;&#x3001;I&#xFF08;KR&#xFF09;&#x306F;&#x3001;&#x4EBA;&#x9593;&#x306E;&#x5FC3;&#x81D3;&#x306E;&#x6D3B;&#x52D5;&#x96FB;&#x4F4D;&#xFF08;APD&#xFF09;&#x306E;&#x5F62;&#x72B6;&#x304A;&#x3088;&#x3073;&#x6301;&#x7D9A;&#x6642;&#x9593;&#x306E;&#x4E3B;&#x8981;&#x306A;&#x6C7A;&#x5B9A;&#x8981;&#x56E0;&#x3067;&#x3042;&#x308B;&#x3002;&#x3057;&#x304B;&#x3057;&#x3001;&#x305D;&#x308C;&#x306F;&#x79C1;&#xFF08;KR&#xFF09;&#x306E;&#x6642;&#x9593;&#x4F9D;&#x5B58;&#x6027;&#x306F;&#x3001;&#x305D;&#x308C;&#x304C;&#x5FC3;&#x81D3;&#x306E;&#x518D;&#x7A81;&#x5165;&#x3068;&#x5FC3;&#x623F;&#x7D30;&#x52D5;&#x306B;&#x95A2;&#x9023;&#x3059;&#x308B;&#x975E;&#x5E38;&#x306B;&#x9AD8;&#x3044;&#x6D3B;&#x6027;&#x5316;&#x5468;&#x6CE2;&#x6570;&#x3067;&#x306E;APD&#x3001;&#x4F1D;&#x5C0E;&#x901F;&#x5EA6;&#xFF08;CV&#xFF09;&#x3001;&#x6CE2;&#x9577;&#xFF08;WL&#xFF09;&#x3092;&#x5236;&#x5FA1;&#x3059;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x307E;&#x3059;&#x304B;&#x3069;&#x3046;&#x304B;&#x306F;&#x4E0D;&#x660E;&#x3067;&#x3042;&#x308B;&#x3002;

&#x65B0;&#x751F;&#x5150;&#x30E9;&#x30C3;&#x30C8;&#x5FC3;&#x5BA4;&#x7B4B;&#x7D30;&#x80DE;&#x5358;&#x5C64;&#x306B;&#x518D;&#x7A81;&#x5165;&#x306E;&#x983B;&#x5EA6;&#x3092;&#x6C7A;&#x5B9A;&#x3059;&#x308B;HERG&#x306E;&#x305F;&#x3081;&#x306B;&#x4E3B;&#x8981;&#x306A;&#x5F79;&#x5272;

&#xAE09;&#xC18D; &#xD55C; &#xC9C0;&#xC5F0;&#xB41C; &#xC815;&#xB958;&#xAE30; &#xCE7C;&#xB968; &#xC804;&#xB958;, I(Kr), &#xC778;&#xAC04;&#xC758; &#xC5D0;&#xD14C;&#xB974;-&#xD55C;-&#xAC00; &#xC11C;-&#xC774;&#xB3D9; &#xAD00;&#xB828; (hERG) &#xCC44;&#xB110;&#xC744; &#xD1B5;&#xD574; &#xD750;&#xB974;&#xB294; &#xBAA8;&#xC591;&#xC758; &#xC8FC;&#xC694; &#xACB0;&#xC815;&#xC790; &#xBC0F; &#xC778;&#xAC04;&#xC758; &#xC2EC;&#xC7A5; &#xD65C;&#xB3D9; &#xC804;&#xC704; (APD)&#xC758; &#xAE30;&#xAC04; &#xC774;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098;, &#xADF8;&#xAC83;&#xC740; &#xC54C; &#xC218; &#xC5C6;&#xC73C;&#xBA74; i(kr)&#xC758; &#xC2DC;&#xAC04; &#xC885;&#xC18D;&#xC131;&#xC744; &#xC5EC;&#xBD80; &#xC81C;&#xC5B4; APD, &#xC804;&#xB3C4; &#xC18D;&#xB3C4; (CV) &#xBC0F; &#xC2EC;&#xC7A5; &#xC7AC;&#xC785;&#xAD6D; &#xBC0F; &#xB3D9; &#xAD00;&#xB828; &#xB41C; &#xB300;&#xB2E8;&#xD788; &#xB192;&#xC740; &#xD65C;&#xC131;&#xD654; &#xC8FC;&#xD30C;&#xC218;&#xC5D0;&#xC11C; &#xD30C;&#xC7A5; (WL) &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC2E0;&#xC0DD;&#xC544; &#xC950; &#xC2EC; &#xC2E4; myocyte &#xB2E8;&#xCE35;&#xC5D0; &#xC7AC;&#xC785;&#xAD6D;&#xC758; &#xC8FC;&#xD30C;&#xC218;&#xB97C; &#xACB0;&#xC815; HERG&#xC5D0; &#xB300; &#xD55C; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;.

el potasio rectificador de corriente r&#xE1;pida retraso, I (Kr), que fluye a trav&#xE9;s del &#xE9;ter-a-go-go los derechos humanos relacionados (hERG) del canal, es un importante determinante de la forma y la duraci&#xF3;n del potencial de acci&#xF3;n cardiaca humana (DPA). Sin embargo, se desconoce si la dependencia del tiempo de I (Kr) le permite controlar APD, la velocidad de conducci&#xF3;n (CV), y longitud de onda (WL) en las frecuencias de activaci&#xF3;n excesivamente altos que son relevantes para la reentrada cardiaca y fibrilaci&#xF3;n.

Un papel importante para HERG de Determinaci&#xF3;n de la frecuencia de la reentrada en monocapa miocitos ventriculares de rata neonatal

Myotonic dystrophy type 1 (DM1), the most common form of muscular dystrophy in adults, results from the expression of toxic gain-of-function transcripts containing expanded CUG-repeats. DM1 patients experience cardiac electrophysiological defects, including prolonged PR-, QRS-, and QT-intervals, that increase susceptibility to sudden cardiac death (SCD). However, the specific biophysical and molecular mechanisms that underlie the electrocardiograph (ECG) abnormalities and SCD in DM1 are unclear. Here, we addressed this issue using a novel transgenic mouse model that exhibits robust cardiac expression of expanded CUG-repeat RNA (LC15 mice). ECG measurements in conscious LC15 mice revealed significantly prolonged QRS- and corrected QT-intervals, but a normal PR-interval. Although spontaneous arrhythmias were not observed in conscious LC15 mice under nonchallenged conditions, acute administration of the sodium channel blocker flecainide prolonged the QRS-interval and unveiled an increased susceptibility to lethal ventricular arrhythmias. Current clamp measurements in ventricular myocytes from LC15 mice revealed significantly reduced action potential upstroke velocity at physiological pacing (9 Hz) and prolonged action potential duration at all stimulation rates (1-9 Hz). Voltage clamp experiments revealed significant rightward shifts in the voltage dependence of sodium channel activation and steady-state inactivation, as well as a marked reduction in outward potassium current density. Together, these findings indicate that expression of expanded CUG-repeat RNA in the murine heart results in reduced sodium and potassium channel activity that results in QRS- and QT-interval prolongation, respectively.

Biophysical mechanisms for QRS- and QTc-interval prolongation in mice with cardiac expression of expanded CUG-repeat RNA.

Long QT-Syndrome (LQTS) patients are at risk of arrhythmias and seizures. We investigated whether autonomic and cardiac repolarization measures differed based on LQTS genotypes, and in LQTS patients with vs. without arrhythmias and seizures.

Autonomic and Cardiac Repolarization Lability in Long QT Syndrome Patients.

The platelet phenotype in certain patients and clinical contexts may differ from healthy conditions. We evaluated platelet activation through specific receptors in healthy men and women, comparing this to patients presenting with ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction. Approach and Results: We identified independent predictors of platelet activation through certain receptors and a murine MI model further explored these findings. Platelets from healthy women and female mice are more reactive through PARs (protease-activated receptors) compared with platelets from men and male mice. Multivariate regression analyses revealed male sex and non-ST-segment-elevation myocardial infarction as independent predictors of enhanced PAR1 activation in human platelets. Platelet PAR1 signaling decreased in women and increased in men during MI which was the opposite of what was observed during healthy conditions. Similarly, in mice, thrombin-mediated platelet activation was greater in healthy females compared with males, and lesser in females compared with males at the time of MI.

Sex-Specific Platelet Activation Through Protease-Activated Receptors Reverses in Myocardial Infarction.

FDA Safety Warning on the Cardiac Effects of Lamotrigine: An Advisory From the Ad Hoc ILAE/AES Task Force.

FDA safety warning on the cardiac effects of lamotrigine: An advisory from the Ad Hoc ILAE/AES Task Force.

Identification and successful management of near-lethal ventricular tachycardia in 2q24 deletion-associated developmental and epileptic encephalopathy.

Cardiac Safety of Lamotrigine: Still Awaiting a Verdict.

It is premature for a unified hypothesis of sudden unexpected death in epilepsy: A great amount of research is still needed to understand the multisystem cascade.

20-40% of individuals whose seizures are not controlled by anti-seizure medications exhibit manifestations comparable to epileptic seizures (ES), but there are no EEG correlates. These events are called functional or dissociative seizures (FDS). Due to limited access to EEG-monitoring and inconclusive results, we aimed to develop an alternative diagnostic tool that distinguishes ES vs. FDS. We evaluated the temporal evolution of ECG-based measures of autonomic function (heart rate variability, HRV) to determine whether they distinguish ES vs. FDS.

Heart rate and autonomic biomarkers distinguish convulsive epileptic vs. functional or dissociative seizures.

Voltage-gated potassium channels are expressed throughout the human body and are essential for physiological functions. These include delayed rectifiers, A-type channels, outward rectifiers, and inward rectifiers. They impact electrical function in the heart (repolarization) and brain (repolarization and stabilization of the resting membrane potential). KCNQx and KCNHx encode K7.x and K11.x proteins, which form delayed rectifier potassium channels. KCNQx and KCNHx channelopathies are associated with both cardiac and neuronal pathologies. These include electrocardiographic abnormalities, cardiac arrhythmias, sudden cardiac death (SCD), epileptiform discharges, seizures, bipolar disorder, and sudden unexpected death in epilepsy (SUDEP). Due to the ubiquitous expression of KCNQx and KCNHx channels, abnormalities in their function can be particularly harmful, increasing the risk of sudden death. For example, KCNH2 variants have a dual role in both cardiac and neuronal pathologies, whereas KCNQ2 and KCNQ3 variants are associated with severe and refractory epilepsy. Recurrent and uncontrolled seizures lead to secondary abnormalities, which include autonomics, cardiac electrical function, respiratory drive, and neuronal electrical activity. Even with a wide array of anti-seizure therapies available on the market, one-third of the more than 70 million people worldwide with epilepsy have uncontrolled seizures (i.e., intractable/drug-resistant epilepsy), which negatively impact neurodevelopment and quality of life. To capture the current state of the field, this review examines KCNQx and KCNHx expression patterns and electrical function in the brain and heart. In addition, it discusses several KCNQx and KCNHx variants that have been clinically and electrophysiologically characterized. Because these channel variants are associated with multi-system pathologies, such as epileptogenesis, K7 channel modulators provide a potential anti-seizure therapy, particularly for people with intractable epilepsy. Ultimately an increased understanding of the role of K channels throughout the body will fuel the development of innovative, safe, and effective therapies for people at a high risk of sudden death (SCD and SUDEP).

ArticleTotal : 2	Year
Publication title Cited by 5	2021
Publication title Cited by 2	2025

Article	Year
Ventricular fibrillation: dynamics and ion channel determinants. Circulation journal : official journal of the Japanese Circulation Society\| PubMed ID: 17587732	2007
Spatial distribution of fibrosis governs fibrillation wave dynamics in the posterior left atrium during heart failure. Circulation research\| PubMed ID: 17704207	2007
A major role for HERG in determining frequency of reentry in neonatal rat ventricular myocyte monolayer. Circulation research\| PubMed ID: 20947828	2010
Biophysical mechanisms for QRS- and QTc-interval prolongation in mice with cardiac expression of expanded CUG-repeat RNA. The Journal of general physiology\| PubMed ID: 31968060	2020
Autonomic and Cardiac Repolarization Lability in Long QT Syndrome Patients. Autonomic neuroscience : basic & clinical\| PubMed ID: 32942226	2020
Sex-Specific Platelet Activation Through Protease-Activated Receptors Reverses in Myocardial Infarction. Arteriosclerosis, thrombosis, and vascular biology\| PubMed ID: 33176447	2021
FDA Safety Warning on the Cardiac Effects of Lamotrigine: An Advisory From the Ad Hoc ILAE/AES Task Force. Epilepsy currents\| PubMed ID: 33641454	2021
FDA safety warning on the cardiac effects of lamotrigine: An advisory from the Ad Hoc ILAE/AES Task Force. Epilepsia open\| PubMed ID: 33681647	2021
Identification and successful management of near-lethal ventricular tachycardia in 2q24 deletion-associated developmental and epileptic encephalopathy. Seizure\| PubMed ID: 34161902	2021
Cardiac Safety of Lamotrigine: Still Awaiting a Verdict. Neurology\| PubMed ID: 35260441	2022
It is premature for a unified hypothesis of sudden unexpected death in epilepsy: A great amount of research is still needed to understand the multisystem cascade. Epilepsia\| PubMed ID: 37129136	2023
Heart rate and autonomic biomarkers distinguish convulsive epileptic vs. functional or dissociative seizures. Seizure\| PubMed ID: 37660533	2023
Neurocardiac pathologies associated with potassium channelopathies. Epilepsia\| PubMed ID: 39087855	2024

David S. Auerbach

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