Dokument: Elektrophysiologische Charakteristika und arrhythmogenes remodeling im Mausmodell nach Myokardischämie und Reperfusion
| Titel: | Elektrophysiologische Charakteristika und arrhythmogenes remodeling im Mausmodell nach Myokardischämie und Reperfusion | |||||||
| Weiterer Titel: | Electrophysiological characteristics and arrhythmogenic remodeling in a murine model of myocardial ischemia and reperfusion | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=57206 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20210827-104427-5 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Bartsch, Benedikt [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Hisaki Makimoto [Gutachter] Prof. Dr. Grandoch, Maria [Gutachter] | |||||||
| Stichwörter: | Myokardinfarkt, ventrikuläre Arrhythmie, EPU, ventrikuläre Tachykardie, | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Zusammenfassung
Ventrikuläre Arrhythmien (VA) als Folge einer kardialen Ischämie stellen eine der Haupttodesursachen weltweit dar und sind daher eine große Herausforderung im klinischen Alltag. Aufgrund ähnlicher kardiovaskulärer Eigenschaften ist die Maus vor dem Hintergrund der Fortschritte in der Gentechnik in den Fokus der kardiovaskulären Forschung geraten. Die Bestimmung der ventrikulären Vulnerabilität in der elektrophysiologischen Untersuchung (EPU) stellt sich in Mäusen als Herausforderung dar und bisherige an Menschen etablierte programmierte elektrische Stimulationsprotokolle (PES) zeigten sich nicht sensitiv genug in der Induktion VA in Mäusen. Kürzlich wurde ein modifiziertes Stimulationsprotokoll (Miniburst (MB)) vorgestellt, welches nun im myocardialen Ischämie-Reperfusions-Modell (IR) bei Wildtyp-Mäusen getestet werden sollte. Folgendes sollte dabei untersucht werden: Erstens, die ventrikuläre Vulnerabilität im Mausmodell 7d post IR, zweitens die Effektivität des neuen Stimulationsprotokolls im Vergleich zum herkömmlichen am Menschen etablierten PES. Nach Thoraxeröffnung betrug die Ischämiezeit der IR-Gruppe (n=7) 45 Minuten, in der Sham-Gruppe (n=8) fand nur die Thoraxeröffnung statt. 7d postoperativ erfolgte in leichter Isofluran-Narkose eine in vivo elektrophysiologische Untersuchung (EPU). Vor der Operation sowie zum Zeitpunkt 1d, 2d und 7d fand eine transthorakale Echokardiographie statt. Die Infarktgrößenbestimmung erfolgte planimetrisch nach Gomoris-Trichrome-Färbung ex vivo nach der EPU. In der IR-Gruppe zeigte sich eine eingeschränkte linksventrikuläre Funktion. In der histologischen Untersuchung zeigte sich eine durchschnittliche Infarktgröße von 32 ± 1.5% (SEM) (n=7) des linken Ventrikels 7d nach IR-Operation. In der IR-Gruppe zeigten sich mehr induzierte VA als in der Sham-Gruppe. Es zeigten sich mehr premature ventricular complex (PVC) und ventrikuläre Tachykardien (VT) (< 1 s) in der IR- als in der Sham-Gruppe. In der IR-Gruppe zeigte sich nach Gabe von Isoproterenol keine Erhöhung der ventrikulären Vulnerabilität und keine Herzfrequenzänderungen. Die Inzidenz von VT war mittels MB-Protokoll höher als im PES-Protokoll. Das MB-Stimulationsprotokoll, insbesondere ab vier Extrastimuli, induzierte mehr VA als das PES-Protokoll in IR-Tieren. Insgesamt zeigte sich anhand der Daten eine gesteigerte ventrikuläre Vulnerabilität der IR-Tiere 7d postoperativ. Das MB-Protokoll zeigte sich besser geeignet und effektiver die ventrikuläre Vulnerabilität in diesem Mausmodell zu untersuchen als die bisherigen Protokolle. Das hier angewandte Stimulationsprotokoll kann in Zukunft dazu dienen, die ventrikuläre Vulnerabilität von transgenen Mäusen nach IR-Operation zu untersuchen.Summary (Englisch) Ventricular arrhythmia (VA) due to cardiac ischemia is one of the major causes of death worldwide, thus treatment remains a challenge for physicians. Having grossly similar cardiac properties as humans and given the rise of genetic engineering mice have become a focus of cardiovascular research. Assessing ventricular vulnerability during electrophysiological studies (EPS) in mice remains non-unified and human based programmed electrical stimulation (PES) protocols seems to lack sensitivity for induction of VA in mice. We transferred a recently elaborated modified stimulation protocol (Miniburst (MB)) into an unrestrained mice model of myocardial ischemia and reperfusion (IR). The aim of this study was to investigate: 1) ventricular vulnerability of mice in 7d after IR, 2) efficacy of our stimulation protocol as compared to conventional approach adopted from human PES protocol. Open chest 45 min myocardial IR (n=7) or sham operation (n=8) was performed. At 7d after operation mildly isoflurane sedated mice underwent in vivo EPS to test ventricular vulnerability. Transthoracic echocardiography was conducted at baseline, 1d, 2d and 7d after operation. Myocardial infarction size was calculated by planimetry after gomoris-trichrome stainings ex vivo after EPS. Left ventricular function was reduced after IR compared to sham operation. Histologic analysis showed myocardial infarction size making up 32 ± 1.5% (SEM) (n=7) of the myocardial tissue 7d after IR-operation. IR mice showed significantly higher arrhythmia scores of induced ventricular arrhythmias compared to sham operated mice. The inducibility of premature ventricular complex and ventricular tachycardia (< 1 s) was significantly enhanced in IR mice as compared to sham operated mice. In IR mice, heart rate response under isoprenaline was blunted and Isoprenaline did not aggravate ventricular vulnerability during EPS. Incidence of VT induction among IR mice was considerably higher with MB protocol as compared to conventional PES protocol. MB protocol, particularly coupling of at least four extrastimuli, enhanced ventricular arrhythmia inducibility as compared to conventional PES protocol in IR mice. In conclusion, our data demonstrated that ventricular vulnerability during EPS is enhanced 7d after myocardial IR in mice. The MB protocol is more feasible and effective for the assessment of ventricular vulnerability in this mouse model as compared to the conventional stimulation protocol. This presented modified approach for programmed electrical stimulation may be useful to investigate ventricular arrhythmogenicity in transgenic mice with IR. | |||||||
| Quelle: | ADABAG, A. S., LUEPKER, R. V., ROGER, V. L. & GERSH, B. J. (2010). Sudden cardiac death: epidemiology and risk factors. Nature Reviews Cardiology, 7, 216.
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Validation of the wall motion score and myocardial performance indexes as novel techniques to assess cardiac function in mice after myocardial infarction. Am J Physiol Heart Circ Physiol, 292, H1187-92. ZIPES, D. P. & WELLENS, H. J. (1998). Sudden cardiac death. Circulation, 98, 2334-51. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Bezug: | 2017-2021 | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 27.08.2021 | |||||||
| Dateien geändert am: | 27.08.2021 | |||||||
| Promotionsantrag am: | 31.03.2021 | |||||||
| Datum der Promotion: | 26.08.2021 |
