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Johansen 2011 Acta Physiol Scand

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Johansen D, Sanden E, Hagve M, Chu X, Sundset R, Ytrehus K (2011) Heptanol triggers cardioprotection via mitochondrial mechanisms and mitochondrial potassium channel opening in rat hearts. Acta Physiol Scand 201:435-44.

» PMID: 21070611

Johansen D, Sanden E, Hagve M, Chu X, Sundset R, Ytrehus K (2011) Acta Physiol Scand

Abstract: Aim: To investigate mechanisms behind heptanol (Hp)-induced infarct size reduction and in particular if protection by pre-treatment with Hp is triggered through mitochondrial mechanisms.

Methods: Langendorff perfused rat hearts, isolated mitochondria and isolated myocytes were used. Infarct size, mitochondrial respiration, time to mitochondrial permeability transition pore (MPTP) opening and AKT and glycogen synthase kinase 3 beta (GSK-3β) phosphorylation were examined.

Results: Pre-treatment with Hp reduced infarct size from 29.7 ± 3.4% to 12.6 ± 2.1%. Mitochondrial potassium channel blockers 5-hydroxy decanoic acid (5HD) blocking mitoK(ATP) and paxilline (PAX) blocking mitoK(Ca) abolished cardioprotective effect of Hp (Hp + 5HD 36.7 ± 2.9% and Hp + PAX 40.2 ± 2.8%). Hp significantly reduced respiratory control ratio in both subsarcolemmal and interfibrillar mitochondria in a dose-dependent manner (0.5-5.0 mm). The ADP oxygen ratio was also significantly reduced by Hp (2 mm). Laser scanning confocal microscopy of tetramethylrhodamine-loaded isolated rat myocytes using line scan mode showed that Hp increased time to MPTP opening. Western blot analysis showed that pre-treatment with Hp increased phosphorylation of AKT and GSK-3β before ischaemia and after 30 min of global ischaemia.

Conclusion: Pre-treatment with Hp protects the heart against ischaemia-reperfusion injury. This protection is most likely mediated via mitochondrial mechanisms which initiate a signalling cascade that converges on inhibition of opening of MPTP. Keywords: Cardioprotection, Gap junction, Heptanol, Ischaemia, Mitochondria, Potassium channels

O2k-Network Lab: NO Tromsoe Larsen TS


Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Heart  Preparation: Isolated mitochondria 

HRR: Oxygraph-2k