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Cardioprotective effects of propofol in isolated ischemia-reperfused guinea pig hearts: role of KATP channels and GSK-3β

Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

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Abstract

Purpose: Propofol exerts cardioprotective effects, but the involved mechanisms remain obscure. The present study examines the cardioprotective effects of propofol and its role in cardiac function, including its effect on KATP channel opening and the inhibition of GSK-3ß activity in ischemia-reperfused hearts.

Methods: Ischemia-reperfusion (I/R) was produced in isolated guinea pig hearts by stopping coronary perfusion for 25 min, followed by reperfusion. The hearts were incubated for ten minutes, with or without propofol (25 or 50 µM), or for five minutes with 500 µM 5-hydroxydecanoate (a mitochondrial KATP channel blocker) or 30 µM HMR1098 (sarcolemmal KATP channel blocker), followed by five minutes with 50 µM propofol before ischemia. Action potentials on the anterior epicardial surface of the ventricle were monitored using a high-resolution charge-coupled device camera system, and at five minutes after reperfusion, GSK-3ß phosphorylation at the serine residue, Ser9, was examined.

Results: After 35 min of reperfusion, propofol (25 and 50 µM) blunted the adverse effects of I/R and reduced infarct size (P<0.05). In addition, prior incubation with 5-hydroxydecanoate or HMR1098 had no effect on functional recovery improved by 50 µM propofol. At five minutes after reperfusion, propofol (25 and 50 µM) shortened the duration of the action potential and increased the levels of phospho-GSK-3ß (P<0.05).

Conclusions: Propofol enhanced mechanical cardiac recovery and reduced infarct size. The data further suggest that GSK-3ß play an important role in propofol cardioprotective actions during coronary reperfusion, but mitochondrial KATP channels do not.

Résumé

Objectif: Le propofol exerce des effets cardioprotecteurs, mais les mécanismes sous-jacents demeurent obscurs. Cette étude examine les effets cardioprotecteurs du propofol et son rôle dans la fonction cardiaque, notamment son effet sur l’ouverture du canal KATP et l’inhibition de l’activité du GSK-3β dans des coeurs ischémiques puis reperfusés.

Méthode: L’ischémie reperfusion (I/R) a été provoquée dans des coeurs isolés de cobayes en interrompant la per fusion coronarienne pendant 25 min, puis en les reperfusant. Les coeurs ont été incubés pendant dix minutes, avec ou sans propofol (25 ou 50 µM), ou pendant cinq minutes avec 500 µM de 5-hydroxydecanoate (un bloqueur du canal KATP mitochondrial) ou 30 µM de HMR1098 (un bloqueur du canal KATP sarcolemmal), suivi par cinq minutes avec 50 µM de propofol avant l’ischémie. Les potentiels d’action sur la surface épicardique antérieure du ventricule ont été surveillés à l’aide d’un système de caméra à dispositif à transfert de charge et, cinq minutes après la reperfusion, la phosphorylation du GSK-3β au résidu de sérine, Ser9, a été examiné.

Résultats: Après 35 min de reperfusion, le propofol (25 et 50 µM) a émoussé les effets négatifs de l’I/R et réduit la taille de l’infarctus (P<0,05). De plus, l’incubation antérieure avec le 5-hydroxydecanoate ou l’HMR1098 n’a pas eu d’effet sur la récupération fonctionnelle améliorée par 50 µM de propofol. Cinq minutes après la reperfusion, le propofol (25 et 50 µM) a abrégé la durée du potentiel d’action et augmenté les niveaux de phospho-GSK-3β (P<0,05).

Conclusion: Le propofol a amélioré la récupération cardiaque mécanique et réduit la taille de l’infarctus. Les données suggèrent aussi que le GSK-3β joue un rôle important dans les actions cardioprotectrices du propofol pendant la reperfusion coronarienne, mais pas les canaux KATP mitochondriaux.

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Author information

Correspondence to Noriaki Kanaya md phd.

Additional information

This study was supported in part by grants-in-Aid (No. C-12671487 and B-15390477) from the Japan Society for the Promotion of Science, Tokyo, Japan.

Competing interests: None declared.

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Kamada, N., Kanaya, N., Hirata, N. et al. Cardioprotective effects of propofol in isolated ischemia-reperfused guinea pig hearts: role of KATP channels and GSK-3β. Can J Anesth 55, 595 (2008). https://doi.org/10.1007/BF03021433

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Keywords

  • KATP Channel
  • Cardioprotective Effect
  • Landiolol
  • Reduce Infarct Size
  • mPTP Opening