Bedeutung von Prostaglandinen und anderen Eicosanoiden für das Verhalten der Mikrozirkulation beim Schock

Zusammenfassung

Eicosanoide (Prostaglandine, Thromboxane, Fessäureperoxyde, Hydroxyfettsäuren, Leukotriene) sind eine heterogene Gruppe von Substanzen, die sich aus der gemeinsamen Vorstufe Arachindonsäure herleiten lassen. Sie warden nicht gespeichert, sondern bei geeigneten (Membran-) Reizen de novo synthetisiert und freigesetzt. Damit ist der Gewebe- bzw. Plasmaspiegel der Substanzen dem Ausmaϐ der Synthese gleichzusetzen und daher durch Syntheseinhibitoren leicht zu beeinflussen. Hierzu gehören neben Glukokortikoiden vor allem nichtsteroidale Antiphlogistika. Der wesentliche Unterschied zwischen beiden Substanzklassen ist, daϐ Glukokortikoide im Zusammenhang mit ihrer membranstabilistierenden Wirkung auch die Synthese aller Eicosanoide hemmen, während nichsteroidale Antiphlogistike nur die Bildung von Prostaglandinen und Thrombozanen inhibieren, aber die Bildung von Leukotrienen und analogen Verbindungen durch erhöhtes Subtratangeboteher erhöhen.

Die heute vorliegenden Untersuchungen über Eicosanoide beim Schock stamen ausschieϐlich aus Tierversuchen. Dabei wird bei allen Modellen eine Zunahme der Eicosanoidbildung gefunden. Hierbei spielen Zyklooxygenaseprodukte offensichtlich eine Rolle bei der für viele Schockformen typischen initialen pulmonalen Hypertension (z. B. PGF2α, thromboxan A2), während die Permeabilitätsstörungen in der Mikrozirkulation eher auf Lipoxygenaseprodukte (Hydroxysäuren, Leukotriene) bezogen warden. Neode Sinstamzklas sen förern insgesamt die Thrombozyten und Graunlozytenaggregation und können damit die Perfusionsstörung der Mikrozirkulation weiter verschlechtern.

Zyklooxygenaseinhibitoren (Azetylsalizylsäure, Indometzin u.a.) hemmen bei prophylaktischer Gabe den pulmonalen Druckanstieg, führen aber eher zu einer Verstärkung der Permeabilitätsstörung. Hier sind günstige Effekte von Glukokortikoiden sowie von Lipoxygenaseinhibitoren oder Antagonisten von Wirkungen dieser Substanzen zu erwarten und tierexperimentell beschrieben. Hierzu gehört auch die Beseitigung freier Sauerstoffradikale, die die nichtenzy matische Fettsäureperoxydation und damit die Bildung gewebetoxischer Substanzen fördern.

Auch Prostaglandine selbst sind therapeutisch bei verschiedenen tierexperimentellen Schockformen (Endotoxin, hämorrhagisch, traumatisch) eingesetzt worden. Günstige Effekte wurden für Inhibitoren der Thromboxansynthese und vor allem für Prostazyklin beschireben. Eline einheitliche und allgemein akzeptierte Erklärung dieser protektiven Effekte existiert bisher nicht, Auch ist die relative Bedeutung solcher Mechanismen beim Vergleich mit »konventionellen« Maϐnahmen der symptomatischen Schocktherapie noch zu definieren.

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