Preconditioning or postconditioning with 8-Br-cAMP-AM protects the heart against regional ischemia and reperfusion: a role for mitochondrial permeability transition

Igor Khaliulin*, Raimondo Ascione, Leonid Maslov, Haitham Amal, M-Saadeh Suleiman

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

The cAMP analogue 8-Br-cAMP-AM (8-Br) confers marked protection against global ischae-mia/reperfusion of isolated perfused heart. We tested the hypothesis that 8-Br is also protective under clinically relevant conditions (regional ischaemia) when applied either before ischemia or at the beginning of reperfusion, and this effect is associated with the mitochondrial permeability transition pore (MPTP). 8-Br (10 μM) was administered to Langendorff-perfused rat hearts for 5 min either before or at the end of 30 min regional ischaemia. Ca2+-induced mitochondria swell-ing (a measure of MPTP opening) and binding of hexokinase II (HKII) to mitochondria were as-sessed following the drug treatment at preischaemia. Haemodynamic function and ventricular arrhythmias were monitored during ischaemia and 2 h reperfusion. Infarct size was evaluated at the end of reperfusion. 8-Br administered before ischaemia attenuated ventricular arrhythmias, improved haemodynamic function, and reduced infarct size during ischaemia/reperfusion. Ap-plication of 8-Br at the end of ischaemia protected the heart during reperfusion. 8-Br promoted binding of HKII to the mitochondria and reduced Ca2+-induced mitochondria swelling. Thus, 8-Br protects the heart when administered before regional ischaemia or at the beginning of reper-fusion. This effect is associated with inhibition of MPTP via binding of HKII to mitochondria, which may underlie the protective mechanism.
Original languageEnglish
Article number1223
Number of pages19
JournalCells
Volume10
Issue number5
DOIs
Publication statusPublished - 17 May 2021

Keywords

  • cyclic AMP
  • heart
  • regional ischaemia
  • cardioprotection
  • reperfusion injury
  • mitochondria per-meability transition pore
  • hexokinase II

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