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Aktuelle Ernährungsmedizin 2005; 30(2): 93-98
DOI: 10.1055/s-2004-834734
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© Georg Thieme Verlag KG Stuttgart · New York

Auswirkung von Hyperglykämie und Diabetes auf die ischämische Präkonditionierung

Effect of Hyperglycaemia and Diabetes Mellitus on Ischaemic PreconditioningD.  Ebel1 , B.  Preckel1 , W.  Schlack1
  • 1Klinik für Anästhesiologie, Universitätsklinikum Düsseldorf
Manuskript nach einem Vortrag bei dem 22. Gemeinsamen Kongress von DGEM, AKE und GESKES ernährung 2004 in München vom 6. - 8.6.2004
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Publication Date:
14 April 2005 (online)

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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

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40001 Düsseldorf

Phone: + 49/211/81-18101

Fax: + 49/211/81-16253

Email: ebeld@uni-duesseldorf.de