Dokument: Charakterisierung der erythrozytären Funktion in der Anämie bei Patienten mit akutem ST-Hebungsinfarkt

Titel:

Charakterisierung der erythrozytären Funktion in der Anämie bei Patienten mit akutem ST-Hebungsinfarkt

Weiterer Titel:

Characterization of erythrocyte function in anemia in patients with acute ST-elevation myocardial infarction

URL für Lesezeichen:

https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=72139

URN (NBN):

urn:nbn:de:hbz:061-20260209-132738-4

Kollektion:

Dissertationen

Sprache:

Deutsch

Dokumententyp:

Wissenschaftliche Abschlussarbeiten » Dissertation

Medientyp:

Text

Autor:

Langerbein, Caroline [Autor]

Dateien:

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Dateien vom 03.02.2026 / geändert 03.02.2026

Beitragende:

Prof. Dr. Kelm, Malte [Gutachter]
Prof. Dr. Germing, Ulrich [Gutachter]

Dewey Dezimal-Klassifikation:

600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit

Beschreibungen:

Rationale: Kardiovaskuläre Erkrankungen, einschließlich des Myokardinfarkts (MI), stellen in Deutschland die führende Todesursache dar. Eine häufig begleitende Komplikation ist die Anämie, die mit einer ungünstigen Prognose assoziiert sein kann. Der Zusammenhang zwischen einer Anämie, dem daraus resultierenden zirkulierenden Stickstoffmonoxid (NO) – Pool und der Mortalität nach einem Myokardinfarkt ist bisher jedoch nicht abschließend geklärt.
Zielsetzung: Ziel dieser Arbeit ist es, die Rolle der Anämie im Rahmen eines ST- Hebungsinfarkt (STEMI) zu analysieren. Im Fokus stehen dabei insbesondere die Funktionen der Erythrozyten, sowie deren Einfluss auf die endotheliale Stickstoffmonoxid-Synthase (eNOS). Untersucht werden soll zudem, wie sich diese Faktoren auf die Funktion des linken Ventrikels nach Ischämie-/Reperfusionsschaden auswirken.
Hypothese: Wir nehmen an, dass die Anämie bei Patienten mit akutem Myokardinfarkt eine Änderung des zirkulierenden NO-Pools verursacht und die kardioprotektiven Eigenschaften der Erythrozyten verringert.
Methoden und Resultate: Im murinen Langendorff-Modell wurde der Einfluss von Erythrozyten, sowie von Plasma anämischer und nicht-anämischer Patienten mit ST- Hebungsinfarkt auf die kardiale Erholung nach Ischämie/Reperfusion untersucht. Die Messung der kardialen linksventrikulären Kontraktilität erfolgte anhand des linksventrikulären Druckgradienten (LVDP) und die über den LVDP abgeleitete Geschwindigkeit der Kontraktion (+dp/dt) und der Relaxation (-dp/dt). Des Weiteren wurde auch der Einfluss einer präischämischen chronischen und subakuten Anämie im Mausmodell untersucht.
Humane Erythrozyten von Patienten mit STEMI verschlechterten die kontraktile Erholung nach myokardialer Ischämie und anschließender Reperfusion im Langendorff-Modell signifikant bei zusätzlichem Vorliegen einer Anämie. Bei Verwendung von Plasma zeigten sich keine Unterschiede in Abhängigkeit vom Auftreten einer Anämie.
Schlussfolgerungen: Zusammengefasst lässt sich feststellen, dass eine milde, normozytäre und normochrome Anämie mit einer gestörten Funktion der Erythrozyten sowie einer reudzierten Konzentration zirkulierenden Stickstoffmonoxids assoziiert ist. Erythrozytäre und endotheliale Stickstoffmonoxid-Synthase spielen dabei eine zentrale Rolle in der zugrundeliegenden Kausalkette. Die vorliegenden Ergebnisse deuten darauf hin, dass eine Dysfunktion der Erythrozyten und eine verminderte eNOS-Aktivität im Rahmen eines akuten Myokardinfarkts potenziell zu einer ungünstigeren klinischen Prognose beitragen können.

Rationale: Cardiovascular diseases, including myocardial infarction (MI), are the most common causes of death in Germany. Anemia is a common comorbidity, which can negatively impact the prognosis of these patients. The relationship between anemia, the resulting circulating nitric oxide (NO) pool, and mortality after MI remains unclear.
Objective: This study aims to examine the impact of anemia in ST-elevation myocardial infarction. Red blood cell function, the effects on endothelial nitric oxide synthase, and the resulting alterations in left ventricular function after ischemia/reperfusion injury will be analyzed.
Hypothesis: We hypothesize that anemia in patients with acute MI causes a change in the circulating NO pool and reduces the cardioprotective properties of erythrocytes.
Methods and results: In the murine Langendorff model, the influence of red blood cells and plasma from anemic and non-anemic patients with ST-elevation myocardial infarction on cardiac recovery after ischemia/reperfusion was investigated. Cardiac left ventricular contractility was measured using the left ventricular pressure gradient (LVDP) and the velocity of contraction (+dp/dt) and relaxation (-dp/dt). Furthermore, the influence of pre-ischemic chronic and subacute anemia was also analyzed in the mouse model.
Human red blood cells (RBCs) from patients with STEMI significantly impaired contractile recovery following myocardial ischemia and following reperfusion in context of concomitant anemia. When plasma was used, no differences were found depending on the presence of anemia.
Conclusions: In conclusion, mild normocytic, normochromic anemia appears to be associated with impaired erythrocyte function and a concomitant reduction in circulating nitric oxide (NO) bioavailability. Erythrocyte-derived and endothelial nitric oxide synthase (eNOS) contribute significantly to this pathophysiological cascade. The data suggests that dysfunction of erythrocytes and diminished eNOS activity in the setting of acute myocardial infarction may exacerbate ischemia-reperfusion injury and negatively impact left ventricular function and overall clinical outcomes.

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