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Preconditioning or Postconditioning with 8-Br-cAMP-AM Protects the Heart against Regional Ischemia and Reperfusion: A Role for Mitochondrial Permeability Transition

1
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Pharmacy Building, Ein Karem, Jerusalem 91120, Israel
2
Bristol Medical School (THS), Faculty of Health Sciences, University of Bristol, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK
3
Cardiology Research Institute, Tomsk National Research Medical Center, The Russian Academy of Sciences, 111 a, Kievskaya Street, 634012 Tomsk, Russia
*
Author to whom correspondence should be addressed.
Academic Editor: Stephen Yarwood
Cells 2021, 10(5), 1223; https://doi.org/10.3390/cells10051223
Received: 27 April 2021 / Revised: 12 May 2021 / Accepted: 13 May 2021 / Published: 17 May 2021
(This article belongs to the Special Issue Cyclic AMP/PKA/Epac Signaling in Cardiovascular Health and Disease)
The cAMP analogue 8-Br-cAMP-AM (8-Br) confers marked protection against global ischaemia/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 swelling (a measure of MPTP opening) and binding of hexokinase II (HKII) to mitochondria were assessed 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. Application 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 reperfusion. This effect is associated with inhibition of MPTP via binding of HKII to mitochondria, which may underlie the protective mechanism. View Full-Text
Keywords: cyclic AMP; heart; regional ischaemia; cardioprotection; reperfusion injury; mitochondria permeability transition pore; hexokinase II cyclic AMP; heart; regional ischaemia; cardioprotection; reperfusion injury; mitochondria permeability transition pore; hexokinase II
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MDPI and ACS Style

Khaliulin, I.; Ascione, R.; Maslov, L.N.; Amal, H.; Suleiman, M.S. Preconditioning or Postconditioning with 8-Br-cAMP-AM Protects the Heart against Regional Ischemia and Reperfusion: A Role for Mitochondrial Permeability Transition. Cells 2021, 10, 1223. https://doi.org/10.3390/cells10051223

AMA Style

Khaliulin I, Ascione R, Maslov LN, Amal H, Suleiman MS. Preconditioning or Postconditioning with 8-Br-cAMP-AM Protects the Heart against Regional Ischemia and Reperfusion: A Role for Mitochondrial Permeability Transition. Cells. 2021; 10(5):1223. https://doi.org/10.3390/cells10051223

Chicago/Turabian Style

Khaliulin, Igor, Raimondo Ascione, Leonid N. Maslov, Haitham Amal, and M. S. Suleiman 2021. "Preconditioning or Postconditioning with 8-Br-cAMP-AM Protects the Heart against Regional Ischemia and Reperfusion: A Role for Mitochondrial Permeability Transition" Cells 10, no. 5: 1223. https://doi.org/10.3390/cells10051223

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