Neue Strategien in der Kardioprotektion beim akuten Myokardinfarkt: Bedeutung des hypoxischen Nitrat-Nitrit-NO-Stoffwechsels

Zusammenfassung

Der akute Myokardinfarkt mit konsekutiver linksventrikulärer Dysfunktion und Herzinsuffizienz ist weltweit die Hauptursache für kardiovaskuläre Morbidität und Mortalität. Die optimale Therapie des akuten Myokardinfarkts beinhaltet die frühzeitige, erfolgreiche Revaskularisierung des ischämischen Areals. Diese Therapie führt jedoch in Teilen paradoxerweise selbst zu einer Schädigung des Myokards, dem sog. myokardialen Ischämie/Reperfusionsschaden (IRS). Hierdurch wird der Erfolg der frühzeitigen Reperfusion limitiert. Kardioprotektive Strategien verfolgen das Ziel, den IRS zu minimieren, das Risiko der Herzinsuffizienz zu vermindern und die Prognose des Patienten zu verbessern. Die Übertragung der im Rahmen von experimentellen Studien erzielten erfolgsversprechenden Ergebnisse in die klinische Praxis war jedoch bisher enttäuschend. Trotz extensiver Forschung konnte sich kein kardioprotektives Verfahren in der Klinik durchsetzen. Die Modulation des Nitrat-Nitrit-Stickstoffmonoxid (NO)-Stoffwechselweges könnte einen Wendepunkt in der Kardioprotektion darstellen. In einer Reihe präklinischer Studien wurde aufgezeigt, dass die Beeinflussung dieses Signalweges zytoprotektiv wirkt. Erste translationale Untersuchungen sind vielversprechend, während die Ergebnisse großer klinischer Studien noch ausstehen.

Abstract

Acute myocardial infarction remains one of the leading causes of morbidity, mortality and disability in industrialized countries. After an acute myocardial infarction, early and successful myocardial reperfusion is the most effective strategy for reducing the size of a myocardial infarct and improving the clinical outcome. The process of restoring blood flow to the ischemic myocardium, however, can induce injury itself. This phenomenon, termed myocardial ischemia reperfusion injury (IRS), can paradoxically reduce the beneficial effects of myocardial reperfusion. In experimental studies a number of strategies have been shown to ameliorate lethal reperfusion injury. However, the translation of these beneficial effects into the clinical setting has been disappointing. Modulation of the hypoxic nitrate-nitrite-nitric oxide (NO) pathway may have the potential to challenge this problem. First translational studies are promising and clinical trials are ongoing.

Schlüsselwörter

Nitrit - Ischämie - Reperfusionsschaden - Kardioprotektion

Keywords

nitrite - reperfusion damage - cardioprotection

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