Institut for Biomedicin

Jacob Johnsen

Inhibition of KV7 channels protects against myocardial ischemia and reperfusion injury

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisKonferenceabstrakt i tidsskrift

Aims: KV7 channel are activated by ischemia and mediate hypoxic vasodilatation. We investigated the effect of KV7 channel modulation on cardiac ischemia and reperfusion (IR) injury and the interaction with cardioprotection by ischemic preconditioning (IPC).
Methods and Results: We investigated the expression of the KV7 channels in rat hearts by reverse transcriptse PCR. The effect of the KV7 channel inhibitors, XE991 and linopirdine, and the KV7 channel opener, flupirtine on myocardial IR injury in isolated hearts and coronary arteries from Wistar rats was examined. Hearts were subjected to no-flow, global ischemia and reperfusion with and without IPC. Infarct size (IS) was quantified by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hemodynamics were measured using a catheter inserted in the left ventricle. Functional studies on isolated coronary arteries were performed in a wire myograph.
KV7.1, KV7.4 and KV7.5 were expressed in rat coronary arteries and all KV7 subtypes (KV7.1-5) in the left and right ventricles of the heart. KV7 channel blockade by XE991 and linopirdine reduced infarct size additive to infarct reduction by IPC. Flupirtine abolished infarct size reduction by IPC. In isolated coronary arteries XE991 inhibited relaxation during both hypoxia and reoxygenation.
Conclusion: KV7 channel are active during hypoxia and KV7 channel inhibition is cardioprotective. These findings suggest a potential for KV7 blockers in the treatment of ischemia-reperfusion injury although safety should be further addressed.
OriginalsprogEngelsk
TidsskriftActa Physiologica
Vol/bind215
NummerS706
ISSN1748-1708
StatusUdgivet - 21 sep. 2015

    Forskningsområder

  • KV7, Reperfusion, Ischemi, Cardioprotection

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