Zusammenfassung
Patienten mit Diabetes mellitus (DM) erleiden häufiger einen Myokardinfarkt als Nicht-Diabetiker.
Zusätzlich ist bei diesen Patienten nach einem Infarkt die Letalität deutlich erhöht
und die Langzeitprognose verschlechtert. Die ischämische Präkonditionierung (PC) ist
der stärkste endogene Protektionsmechanismus des Myokards, bei dem kurze Ischämien
das Herz gegen die Folgen nachfolgender Ischämien schützen. Man unterscheidet hierbei
eine frühe Phase der Protektion (frühe PC, EPC), die sofort nach der präkonditionierenden
Ischämie einsetzt und das Herz für 2 - 3 Stunden schützt, und eine späte Phase der
Protektion (späte PC, LPC), die nach 12 - 24 Stunden einsetzt und dann mehrere Tage
anhält. Ursache für die schlechte Prognose von Diabetikern mit Myokardinfarkt könnte
die Blockade des myokardialen Schutzes durch PC sein. So ist im Gegensatz zu Nicht-Diabetikern
bei Infarktpatienten mit DM eine Präinfarktangina nicht mit einem verringerten Zellschaden,
besserer linksventrikulärer Funktion oder reduzierter Letalität assoziiert. Tierexperimentell
konnte gezeigt werden, dass eine kurzfristige Hyperglykämie und ein DM sowohl die
Protektion durch EPC als auch durch LPC aufheben. Es wird vermutet, dass die Blockade
mitochondrialer ATP-sensitiver Kaliumkanäle (KATP) durch die Hyperglykämie hier eine wichtige Rolle spielen. Allerdings gibt es Hinweise,
dass ein DM an weiteren Stellen in die Signaltransduktionskaskade der Präkonditionierung
eingreift. Der Schutz durch LPC konnte nach einer kurzfristigen Blutzuckersenkung
mit Insulin nicht wiederhergestellt werden, während eine längere 2-wöchige Insulintherapie
sowohl den Schutz von EPC als auch von LPC rekrutieren konnte. Da die Aufhebung der
PC auch beim Menschen wahrscheinlich ist, könnte dies die schlechte Prognose von Diabetikern
nach Myokardinfarkt zumindest teilweise erklären. Zum Verständnis des Mechanismus
dieser Blockade sind weitere Untersuchungen notwendig.
Abstract
The incidence of myocardial infarction (MI) in patients with diabetes mellitus (DM)
is higher than in patients without DM. Additionally, mortality is higher and long-term
prognosis is worse in diabetic patients with MI compared with non-diabetic patients.
Ischaemic preconditioning (PC) which is triggered by a short period of ischaemia (like
during angina) is the strongest endogenous mechanism protecting the myocardium against
the consequences of a subsequent ischaemia. There are two phases of protection: an
early phase (early PC, EPC), which starts immediately after the preconditioning ischaemia
and lasts for 2 - 3 hours; and a late phase of protection starting after 12 - 24 hours
and lasting for days (late PC, LPC). A blockade of the protection provided by PC may
be the cause for the poor prognosis of diabetic patients with MI. In contrast to patients
without DM, in diabetic patients, pre-infarct angina is not associated with smaller
cellular damage, better left ventricular performance, or reduced mortality. In animal
studies, it was shown that short-term hyperglycaemia and DM abolish the protection
by EPC as well as LPC. It is assumed that the inhibition of ATP-sensitive potassium
channels (KATP) by hyperglycaemia plays an important role in this setting. However, some findings
suggest that this is not the only site of blockade in the signal transduction cascade
of PC. The protection by LPC could not be restored by short-term insulin treatment,
while protection by both EPC and LPC was restored after two weeks of insulin treatment.
The blockade of PC is also very likely in diabetic patients and may even partly explain
the poor prognosis of these patients after MI. Further studies are needed to elucidate
the mechanism of the blockade of PC.
Schlüsselwörter
Diabetes mellitus - Hyperglykämie - ischämische Präkonditionierung - Myokardischämie
- Myokardinfarkt
Key words
Diabetes mellitus - hyperglycaemia - ischaemic preconditioning - myocardial ischaemia
- myocardial infaction
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Dr. med. Dirk Ebel
Klinik für Anästhesiologie · Universitätsklinikum Düsseldorf
Moorenstraße 5
Postfach 101007
40001 Düsseldorf
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Fax: + 49/211/81-16253
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