The significance of the washout period in preconditioning

Salie, Ruduwaan; Lochner, Amanda; Loubser, D

doi:10.1111/1755-5922.12252

Cited by 2 publications

(2 citation statements)

References 60 publications

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“…The requirement for PKB activation in cardioprotection was first demonstrated by Tong et al who reported that its inhibition during a preconditioning stimulus abolished protection. These results were subsequently confirmed by Salie et al . The role of ERK activation during preconditioning was less certain, and conflicting data were reported …”

Section: Risk Pathwaymentioning

confidence: 56%

Melatonin and cardioprotection against ischaemia/reperfusion injury: What's new? A review

Lochner

Marais

Huisamen

2018

Journal of Pineal Research

Self Cite

101

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Melatonin is a pleiotropic hormone with several functions. It binds to specific receptors and to a number of cytosolic proteins, activating a vast array of signalling pathways. Its potential to protect the heart against ischaemia/reperfusion damage has attracted much attention, particularly in view of its possible clinical applications. This review will focus mainly on the possible signalling pathways involved in melatonin-induced cardioprotection. In particular, the role of the melatonin receptors and events downstream of receptor activation, for example, the reperfusion injury salvage kinase (RISK), survivor activating factor enhancement (SAFE) and Notch pathways, the sirtuins, nuclear factor E2-related factor 2 (Nrf2) and translocases in the outer membrane (TOM70) will be discussed. Particular attention is given to the role of the mitochondrion in melatonin-induced cardioprotection. In addition, a brief overview will be given regarding the status quo of the clinical application of melatonin in humans.

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Section: Risk Pathwaymentioning

confidence: 56%

Melatonin and cardioprotection against ischaemia/reperfusion injury: What's new? A review

Lochner

Marais

Huisamen

2018

Journal of Pineal Research

Self Cite

101

View full text Add to dashboard Cite

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“…Apparently, a short (5 min) washout period, or its absence, determines the impact of the elevated cAMP on the myocardial injury during I/R. Thus, Salie et al [ 47 ] have recently shown in experiments on isolated rat heart that during the 5 min washout period after IP induced by a 5 min global ischaemia, activation of the cell survival kinases, such as p38MAPK, JNKp54/p46, Akt and extracellular signal-regulated kinase (ERK), takes place that might determine the cardioprotective effect of PKA. Others have suggested that the cAMP-dependent antiarrhythmic effect of IP is mediated by enhancing vagal influences [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

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

Khaliulin

Ascione

Маслов

et al. 2021

Cells

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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.

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The significance of the washout period in preconditioning

Abstract: PKA activation before regional ischaemia is a prerequisite for cardioprotection in both B2PC and IPC. However, ROS was crucial only in IPC. Kinase activation during the washout phase of IPC and B2PC, albeit different, affords the same cardioprotective response.

Cited by 2 publications

References 60 publications

Melatonin and cardioprotection against ischaemia/reperfusion injury: What's new? A review

Melatonin and cardioprotection against ischaemia/reperfusion injury: What's new? A review

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

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