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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
521

Dois tipos de memórias contráteis em miocárdio de mamífero

Souza, Rejane Cardoso 31 March 2011 (has links)
In the heart, the existence of an electrical memory was firstly reported by Rosenbaum et al. (1982), but Rios et al. (1975) and Garcia Moreira (1977) were those that firstly described the existence of contractile memories in the amphibian myocardium. These authors developed a mathematical model for representing such phenomenon. In the present study, we aimed to characterize two kinds of contractile memories occurring in the mammalian myocardium. One of them, depresses the tissue (the depressant memory, DM) and the other one acts by stimulating it (the excitatory memory, EM). The pivotal rationale guiding this work was: when the heart is challenged by changing the environment sources like nutrients, chemicals, temperature, etc., its behavior changes in order to optimize the energy expenditure associated with its contractility. This adaptation process allows to be reached a new state of dynamic equilibrium. In order to express such behavior, the tissue creates contractile memories for adjusting the amplitude of myocardial forces. This is provided by balancing the load of DM and EM available at each myocardial beat. The expression and accumulation of these memories were studied in the guinea pig atria submitted to the experimental protocols described previously by Seed & Walker (1988), Shimizu (2000), and Conde-Garcia (not published). The expression and accumulation of myocardial memories were described by employing two static descriptors, LODMmax and LOEMmax. They stand for the maximum load of depressant memory and the maximum load of excitatory memory, respectively. Furthermore, another pair of dynamic descriptors was also used to measure the maximum rate of erasing of the depressant memory (MREDM) and the other one to measure the maximum rate of erasing of the excitatory memory (MREEM). The static descriptors represent the transference of load of both memories but the dynamic descriptors were related to the rate of erasing of such memories. Our results brought us onto the following conclusions: 1. contractile memories are a phenomenon apart from the electrical memory because rising the external potassium from 2.7 to 7.0 mM did not modify (n n = 4) LODMmax that changed from 82,09 ± 1,58 to 81,56 ± 2,01% (p > 0,05), LOEMmax from 83,36 ± 0,56 to 90,12 ± 17,92% (p > 0,05), MREDM changed from -1,36 ± 0,67 to -1,13 ± 0,42gf/s (p > 0,05), and MREED from -2,09 ± 1,65 to -1,56 ± 1,41gf/s (p > 0,05). 2. However, the expression and accumulation of DM and EM are affected by the intracellular calcium transient. The increase of extracellular calcium from 1,37 to 5,47mM (n = 3) reduced LODMmax: from 87,56 ± 2,33 to 63,83 ± 3,78% (p < 0,05); LOEMmax from 84,36 ± 0,54 to 13,91 ± 0,11% (p < 0,05); MREDM from -2,58 ± 0,71 to -1,20 ± 0,37gf/s (p < 0,05) and MREEM from -0,90 ± 0,13 to -0,34 ± 0,05 gf/s (p < 0,05). Adding 5mM cafeine to the bath solution also reduced LODMmax from 79,88 ± 3,48 to 56,68 ± 6,62% (p < 0,05); LOEMmax from 77,14 ± 1,02 to 28,54 ± 2,11% (p < 0,05); MREDM from -1,78 ± 0,50 to -0,60 ± 0,10 gf/s (p < 0,05), and MREED from -1,74 ± 0,64 to -0,33 ± 0,14 gf/s (p < 0,05); 3. In the experimental condition employed in this work, a given beat receives both depressant and excitatory information built by the last ten beats. / A capacidade de o miocárdio memorizar foi estudada inicialmente por Rosenbaum (1982), que, entre outros, relataram uma memória elétrica no coração. Todavia, Rios e cols. (1975) e Moreira (1977) foram os primeiros a descrever a existência de memória contrátil no miocárdio de anfíbio. Eles propuseram um modelo matemático para representar esse fenômeno. A nossa proposta, contudo, visou caracterizar dois tipos de memórias contráteis. Uma delas inibe o inotropismo (memória depressora, MD) e a outra, o estimula (memória excitadora, ME). A hipótese central deste trabalho propõe que, quando o coração é desafiado por um novo ambiente (nutrientes, químicos, pH etc.), ele redefine sua atividade contrátil para que possa alcançar um novo estado de equilíbrio. Para expressar tal comportamento, o miocárdio cria memórias, visando ajustar a amplitude das forças geradas. Isto se dá por meio do balanço entre a carga de MD e de ME de cada batimento. Neste trabalho, a expressão e a acumulação destas memórias foram estudadas em átrio de cobaia, utilizando-se dois descritores para cada uma delas um estático, o IKMDmax e IKMEmax, que representam o incremento máximo de carga de MD e ME, respectivamente, e outro dinâmico VmedAMD e VmedAME - que está associado à velocidade de apagamento de cada memórias. As preparações foram ensaiadas com diferentes protocolos experimentais como os descritos por Seed & Walker (1988), Shimizu, et al. (2000) e Conde-Garcia (não publicado). Os resultados mostraram que a memória contrátil difere do fenômeno relativo à memória elétrica do miocárdio, porque, elevando-se o potássio externo de 2,7 para 7,0 mM, não houve variação significativa dos descritores, pois, para n = 3, o IKMDmax passou de 82,09 ± 1,58 para 81,56 ± 2,01% (p > 0,05), o IKMEmax passou de 83,36 ± 0,56 para 90,12 ± 17,92% (p > 0,05), a VmedAMD variou de -1,36 ± 0,67 para -1,13 ± 0,42gf/s (p > 0,05) e a VmedME foi alterada de -2,09 ± 1,65 para -1,56 ± 1,41gf/s (p > 0,05). A expressão e a acumulação das memórias são fenômenos que dependem do transiente intracelular de cálcio nas células miocárdicas. A elevação do cálcio extracelular de 1,37 para 5,47mM, para n = 3, alterou o IKMDmax: de 87,56 ± 2,33 para 63,83 ± 3,78% (p < 0,05); IKMEmax: 84,36 ± 0,54 para 13,91 ± 0,11% (p < 0,05); VmedAMD: -2,58 ± 0,71 para -1,20 ± 0,37gf/s (p < 0,05) e VmedME: -0,90 ± 0,13 para -0,34 ± 0,05 gf/s (p < 0,05). A adição de 5mM de cafeína à solução controle do banho fez o IKMDmax variar de 79,88 ± 3,48 para 56,68 ± 6,62% (p < 0,05); o IKMEmax de 77,14 ± 1,02 para 28,54 ± 2,11% (p < 0,05); a VmedAMD de -1,78 ± 0,50 para -0,60 ± 0,10 gf/s (p < 0,05) e a VmedME -1,74 ± 0,64 para -0,33 ± 0,14 gf/s (p < 0,05). Nas condições experimentais deste estudo, uma dada contração recebe informações depressoras e excitadoras que foram geradas pelos últimos dez batimentos.
522

Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs

Kemter, Elisabeth, Müller, Andreas, Neukam, Martin, Ivanova, Anna, Klymiuk, Nikolai, Renner, Simone, Yang, Kaiyuan, Broichhagen, Johannes, Kurome, Mayuko, Zakhartchenko, Varlie, Kessler, Barbara, Knoch, Klaus-Peter, Bickle, Marc, Ludwig, Barbara, Johnsson, Kai, Lickert, Heiko, Kurth, Thomas, Wolf, Eckhard, Solimena, Michele 09 November 2021 (has links)
The failure of β cells to secrete sufficient amounts of insulin is a key feature of diabetes mellitus. Each β cell secretes only a small amount of insulin upon stimulation in a highly regulated fashion: young insulin is preferentially released, whereas old insulin is mainly degraded within the β cell. How this process is regulated in vivo and likely altered in diabetes is currently unknown. We present here a transgenic pig model that allows the in vivo fluorescent labeling of age-distinct insulin secretory granule pools, hence providing a close-to-life readout of insulin turnover. This will enable the study of alterations in β cell function in an animal model close to humans.
523

Die genetische Varianz des Porzinen Parvovirus und die Wirksamkeit einer neuen experimentellen Vakzine

Foerster, Tessa 30 August 2016 (has links)
Das porzine Parvovirus (PPV), 2013 vom International Committee on taxonomy of Viruses (ICTV) in ungulate Protoparvovirus 1 umbenannt, ist ein unbehülltes, einzelsträngiges DNA Virus und gehört innerhalb der Familie Parvoviridae zur Subfamilie Parvovirinae. Es ist weltweit in allen Bereichen der Schweinehaltung endemisch und verursacht große wirtschaftliche Verluste in den Betrieben (TRUYEN und STRECK 2012). Anders als die verwandten caninen und felinen Parvoviren (seit 2013 arnivore Protoparvovirus 1) ist es nicht durch zum Teil tödlich verlaufende Durchfallerkrankungen, sondern durch Fruchtbarkeitsstörungen wie Abort, Mumifikation und Unfruchtbarkeit, auch bekannt als SMEDI – Syndrom (Stillbirth = Totgeburt, Mummification =Mumifikation, Embryonic Death = embryonaler Tod und Infertility = Unfruchtbarkeit), gekennzeichnet. Die Schwere des Verlaufs hängt dabei wesentlich vom Zeitpunkt sowie von dem, für die Infektion verantwortlichen Isolats ab. Als besonders gefährdet gelten ungeimpfte Jungsauen, die innerhalb der ersten 70 Tage der Trächtigkeit in Kontakt mit dem Virus treten. Das Virus verfügt über eine ausgesprochen hohe Tenazität gegenüber äußeren Einflüssen. Es ist hitzestabil, unempfindlich gegenüber pH-Werten zwischen 3-9 sowie äther- und chloroformresistent (CARTWRIGHT und HUCK 1967, MAYR et al. 1968, JOHNSON und COLLINGS 1969, BACHMANN 1970, MORIMOTO 1972). Einmal im Bestand bleibt es somit über Monate infektiös. Es stehen für die Bekämpfung nur wenige Mittel zur Verfügung. Eine entscheidende Möglichkeit ist die Einhaltung eines strikten Impfregimes, wobei Impfstoffe zum Einsatz kommen, die seit etwa 3 Jahrzehnten auf den gleichen inaktivierten Virus-Isolaten beruhen. In den letzten zehn Jahren wurden zunehmend neue Isolate entdeckt, die sich, wie das hochvirulente Isolat Kresse und das wenig virulente Isolat NADL2, nur in wenigen Aminosäuren unterscheiden. Zum Teil weisen sie aber gravierende Unterschiede in ihrer Pathogenität auf. Daraus ergeben sich neben dem dringenden Rat zur Beobachtung der aktuellen Entwicklung mehrere Fragen hinsichtlich der zukünftigen Handhabung des Virus (SOARES et al. 2003, ZIMMERMANN et al. 2006). So sollte geklärt werden: • wie verbreitet sind diese neuen Isolate • was könnte ihre Entwicklung begünstigt haben • wie effizient ist der Schutz, den herkömmliche Impfstoffe gegen die neuen Isolate bieten • kann eines der Isolate eine Grundlage für einen neuen, effizienteren Impfstoff liefernDiese Dissertation umfasst insgesamt drei Veröffentlichungen, welche versuchen, die gestellten Fragen zu beantworten. Im ersten Artikel wird die Wirksamkeit eines neuen Impfstoffes auf Grundlage des hochvirulenten, vorherrschenden Isolat 27a untersucht. Im zweiten Manuskript wird mit Hilfe von in vitro- und in silico- Modellen die Populationsdynamik demonstriert. Die dritte Veröffentlichung widmet sich der Beschreibung der neuen Parvotypen (PPV2, PPV3 und PPV4), welche aus Herzen und Tonsillen von deutschen, klinisch gesunden Schlachtschweinen isoliert werden konnten.
524

Prophylaxe hypoxisch-entzündlicher Hirnschädigungen bedingt durch die extrakorporale Zirkulation (Herz-Lungen-Maschine) am narkotisierten Schwein

Kühne, Lydia 19 October 2016 (has links)
Diese Arbeit beschäftigt sich mit den Auswirkungen der Herz-Lungen-Maschine auf das Gewebe des Hippocampus in einem Ferkelmodell. Die Tiere untereilte man in 5 Gruppen: „Kontrolle“, „Kontrolle mit Minozyklin“, „HLM pulsatil“, „HLM nicht-pulsatil“, sowie „HLM nicht-pulsatil mit Minozyklin“. Es wurde untersucht, ob eine pulsatile Perfusion Schäden in den Zellen des Hippocampus gegenüber eines nicht-pulsatilen Blutflusses während der extrakorporalen Zirkulation abmildern kann. Des Weiteren überprüfte man neuroprotektive Effekte des Tetrazyklin-Derivates Minozyklin während eines kardiochirurgischen Eingriffes mit Herz-Lungen-Maschine. Während der Operation wurde bei allen Ferkeln eine Hypothermie von 28 °C durchgeführt und die HLM-Zeit betrug 90 Minuten. Die Rekonvaleszenzzeit umfasste 120 Minuten. Minozyklin verabreichte man in den entsprechenden Gruppen sowohl zu Beginn des Versuches (4 mg/kg KM) und nach Abkopplung von der Herz-Lungen-Maschine (2 mg/kg KM) intravenös. Hauptbestandteil der Arbeit waren histologische und immunhistochemische Färbemethoden zur Untersuchung des Hippocampus. Mithilfe eines Mikroskops wurden Veränderungen auf zellulärer Ebene im CA1- und CA3-Areal des Cornu ammonis im Hippocampus ausgewertet. Für die Ergebnisse betrachtet man die Pyramidenzellen des Stratum pyramidale. In der Hämatoxylin-Eosin-Färbung wurden Zellen mit den Eigenschaften „Ödem“, „Eosinophilie“ und „Pyknose“ für jedes Versuchstier gezählt. Mit den immunhistochemischen Färbungen sollten Faktoren für den programmierten Zelltod, für Hypoxie (HIF 1-alpha) und für oxidativen Stress (3-Nitrotyrosin) detektiert werden. Als Marker für Apoptose wählte man den Apoptose-induzierenden Faktor (AIF), cleaved Caspase 3 und Poly(ADP)Ribose (PAR).:Inhaltsverzeichnis 1 Einführung 1.1 Kinderherzchirurgie 1.2 Herz-Lungen-Maschine 1.3 Pathophysiologie der HLM 1.3.1 Inflammationsreaktion 1.3.2 Ischämie 1.3.3 Reperfusion 1.4 HLM und Folgen für das Gehirn 1.5 Neuroprotektive Strategien 1.5.1 Pulsatile Perfusion 1.5.2 Minozyklin 1.6 Hippocampus 2 Aufgabenstellung 3 Tiere, Material und Methoden 3.1 Versuchstiere 3.2 Versuch Teil 1: Operation 3.2.1 Gruppeneinteilung und Versuchsaufbau 3.2.2 Anästhesie 3.2.3 Operation 3.2.3.1 Vorbereitungszeit 3.2.3.2 Kardioplegie 3.2.3.3 Herz-Lungen-Maschine mit nicht-pulsatilen Blutfluss/ pulsatilen Blutfluss 3.2.3.4 Medikation mit Minozyklin 3.2.4 Intraoperatives Monitoring 3.2.4.1 Vitalparameter 3.2.4.2 Arterielle Blut-Gas-Analyse 3.2.4.3 Elektrolyt-Haushalt 3.2.4.4 Laktat- und Glukose-Haushalt 3.3. Versuch Teil 2: Laboruntersuchungen 3.3.1 Einbetten der Proben und Herstellung der Schnittpräparate 3.3.2 Histologie 3.3.2.1 Hämatoxylin-Eosin-Färbung 3.3.3 Immunhistochemie 3.3.3.1 Allgemeines Prinzip 3.3.3.2 Nachweis: Apoptose-induzierender Faktor 3.3.3.3 Nachweis: Hypoxie-induzierter Faktor 1- alpha 3.3.3.4 Nachweis: cleaved Caspase 3 3.3.3.5 Nachweis: 3-Nitrotyrosin 3.3.3.6 Nachweis: Poly(ADP)Ribose 3.3.4 RP-HPLC – Reversed Phase High Performance Liquid Chromatography 3.4 Blutgasanalyse 3.5 Auswertung am Mikroskop 3.6 Statistik 4 Ergebnisse 4.1 Intraoperatives Monitoring 4.2 Arterielle Blutproben 4.3 Arterielles Blut: Laktat-Haushalt 4.4 Ergebnisse der RP-HPLC 4.5 Ergebnisse der Hämatoxylin-Eosin-Färbung 4.6 Ergebnisse der immunhistochemischen Färbungen 4.6.1 Apoptose-induzierender Faktor 4.6.2 Hypoxie-induzierter Faktor 1-alpha 4.6.3 3-Nitrotyrosin 4.6.4 Cleaved Caspase 3 4.6.5 Poly-(ADP)-Ribose 5 Diskussion 5.1 Tiermodell und Versuchsaufbau 5.2 Blutproben 5.3 Herz-Lungen-Maschine und nicht-pulsatiler Blutfluss versus pulsatiler Blutfluss 5.4 Extrakorporale Zirkulation und die Gabe von Minozyklin 5.5 Beantwortung der Fragestellungen 6 Zusammenfassung 7 Literaturverzeichnis 8 Anhang 8.1 Einführung 8.1.1 Kinderherzchirurgie 8.1.2 Pathophysiologie der HLM 8.2 Tiere, Material und Methoden 8.2.1 Operation 8.2.2 Intraoperatives Monitoring 8.2.3 Laboruntersuchungen 8.3 Ergebnisse 8.3.1 Intraoperatives Monitoring 8.3.2 Arterielles Blut 8.3.3 Arterielles Blut – Laktat-Haushalt 8.3.4 RP-HPLC 8.3.5 Hämatoxylin-Eosin-Färbung 8.3.6 Immunhistochemie 9 Selbständigkeitserklärung 10 Lebenslauf 11 Koautorenschaft 12 Danksagung
525

Monitorování vývoje onemocnění Huntingtonovy choroby u transgenních miniprasat s N-terminální částí lidského mutovaného huntingtinu: biochemické a motorické změny u F0, F1 a F2 generace / Monitoring of the development of the Huntington's disease in transgenic minipigs with N-terminal part of human mutated huntingtin: biochemical and motoric changes of F0, F1 and F2 generation

Kučerová, Šárka January 2017 (has links)
Huntington's disease (HD) belongs to neurodegenerative disorders. It is a monogenic disease caused by trinucleotic CAG expansion in exon 1 of gene coding protein huntingtin. Even though the cause of HD is known since 1993, the pathophysiology and cure for HD reminds to be found. The animal models are being used for better understanding of HD. The most common animal models for HD are rodents, especially mice but it was also important to create large animal models, which will be more like human. Therefore, TgHD minipig was created in Academic of Science in Liběchov in 2009. This model was created by microinjection of lentiviral vector carrying N-terminal part of human HTT with 124 repetitive CAG in exon 1. This model is viable and in every generation, is part of the offspring transgenic. In this thesis, I specialized to biochemical and behavioral changes of this model. I compared transgenic and wild type siblings. I found that biochemical changes are manifested mostly by increased level of mtHtt fragments in testes and brain. In behavioral part of this thesis I established new methods for testing behavioral changes in this model. The introduced methods showed some changes between wild type and transgenic animals at the tested ages but these changes were not significant due to the low number of...
526

Caractérisation de l'effet des adjuvants CpG et toxine choléra sur la réponse immunitaire générée par le fimbriae F4 administré oralement chez le porc

Delisle, Benjamin January 2008 (has links)
Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.
527

Cinétique de la réponse cytokinaire lors d'infections aux Escherichia coli entéropathogènes dans un modèle de culture d'iléon (IVOC) d'origine porcine

Dubois, Maurice Junior January 2008 (has links)
Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.
528

Utilization of Frozen Thawed Semen in Large Black Pigs; Growth and Carcass Characteristics of Large Black Pigs Fed Diets Supplemented With or Without Alfalfa

Katharine G Sharp (9189401) 31 July 2020 (has links)
<p>In recent years conservation of minor livestock breeds has been faced with numerous challenges attributed to decreasing national herd sizes, as well as differences in reproduction and growth. One such minor swine breed, the Large Black pig (LB), is increasingly attractive to small farmers due to their foraging abilities and carcass characteristics. Therefore, the LB pigs have been used in niche pork production systems which market pasture-raised pork products. The LB breed is critically endangered, maintaining a registered breeding population of less than 400 animals, with increasing prevalence of inbreeding and genetic drift. Therefore, the LB breed could benefit from a genetic importation to increase genetic diversity in a national herd with rapidly decreasing animal numbers. A genetic importation would require frozen semen to be brought in from another country for use in breeding U.S. pigs. Frozen-thawed semen (FTS) presents challenges for swine due to the reduced motile sperm cells which negatively impacts fertility. Therefore, the present study evaluated the utilization of FTS in a genetic importation for the LB pig. </p><p>A genetic importation occurred in 2016 where semen from the United Kingdom was used on various farms in the U.S. but resulted in zero piglets born. Therefore, 16 LB sows were donated to Purdue University for research into improving estrous and ovulation synchronization to facilitate FTS utilization. Four breeding replicates were performed where following 14 days of Matrix feeding, OvuGel® was administered at 144 h following last Matrix feeding (LMF) or 96 h in post-weaned sows and two FTS inseminations occurring at: 30 and 36 h, 17 and 23 h, 24 and 30 h, and 24 and 32 h after OvuGel® for replicates 1-4, respectively. Approximately 2.64±0.3 billion motile sperm cells per insemination were utilized in replicates 1-3 with American LB FTS, with replicate 4 utilizing 0.34±0.03 billion motile sperm cells of imported FTS. Follicle diameter (<i>P</i>=0.260), ovulation within 48 h of OvuGel® (<i>P</i>=0.411), and weight prior to breeding (<i>P</i>=0.681) did not influence conception rate, however expression of estrus was determined to significantly influence conception rate (<i>P</i>=0.043). Seventy-five LB piglets were weaned across the first three breeding replicates, with parity 2 sows observed to have larger litter sizes than parity 1 sows (<i>P</i>=0.066).</p> <p>Large Black and Duroc-sired (DS) crossbred pigs from replicates 1 and 2 farrowing were fed corn and soybean meal based finishing diets supplemented with (FIB) or without alfalfa and wheat middlings (CON). Following 6 dietary phases through finishing, 25 LB and 25 DS pigs were slaughtered at similar ages for digestive organ dissection and carcass measurements. Loin muscles were evaluated for fresh pork quality and instrumental color and tenderness. LB pigs had a reduced ADG (<i>P</i><0.0001) and G:F (<i>P</i><0.0001) compared to DS pigs. Pigs fed FIB resulted in reduced ADG (<i>P</i>=0.020) and reduced G:F (<i>P</i>=0.007). At slaughter LB pigs were 26.4 kg lighter than DS pigs (<i>P</i><0.0001), and pigs that were fed FIB had lighter live weights (<i>P</i>=0.002) than pigs fed CON. LB pigs had 28.5±1.3 cm<sup>2</sup> smaller longissimus muscle area (<i>P</i><0.0001), yielding 2.0 cm more 10<sup>th</sup> rib back fat than DS pigs (<i>P</i><0.0001). CON pigs had heavier HCW (<i>P</i><0.0001) than FIB pigs, however FIB pigs had greater percent lean (<i>P</i>=0.015). LB pigs had significantly reduced percent lean than DS pigs (<i>P</i><0.0001). LB pigs had loins with reduced drip loss (<i>P</i>=0.009) and cooked shear force values (<i>P</i><0.0001). Overall, the growth and carcass composition of the pigs was most affected by genotype, and to a lesser extent than the type of diet fed. </p> <p>In conclusion, the genetic importation of LB semen was successful as ½ blood piglets were created for dispersal into the U.S. LB herd. Improvements in FTS utilization in this heritage breed contributed to the successful creation of live-born pigs. Additionally, growth and carcass information was obtained for LB breeders to use in understanding and marketing of this heritage breed of pigs.</p>
529

Vagus Nerve Stimulation Mitigates Intrinsic Cardiac Neuronal Remodeling and Cardiac Hypertrophy Induced by Chronic Pressure Overload in Guinea Pig

Beaumont, Eric, Wright, Gary L., Southerland, Elizabeth M., Li, Ying, Chui, Ray, KenKnight, Bruce H., Andrew Armour, J., Ardell, Jeffrey L. 01 May 2016 (has links)
Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15–20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling.
530

Vagus Nerve Stimulation Mitigates Intrinsic Cardiac Neuronal and Adverse Myocyte Remodeling Postmyocardial Infarction

Beaumont, Eric, Southerland, Elizabeth M., Hardwick, Jean C., Wright, Gary L., Ryan, Shannon, Li, Ying, KenKnight, Bruce H., Andrew Armour, J., Ardell, Jeffrey L. 01 January 2015 (has links)
This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions.

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