Oestrogen plays a permissive role in cardioprotection

Abstract

Ischaemic preconditioning (IPC) is a powerful cardioprotective intervention. It can salvage upwards of 75% of the myocardium destined to otherwise infarct. This potent cardioprotective strategy has been observed in all animal species examined to date including mammals and birds.1 We have observed IPC's protection in non-human primates (unpublished observation) and strong evidence exists of its efficacy in man.2,3 Since the initial description of IPC in 1986 by Murry et al. ,4 many investigators have toiled to uncover its mechanism in the hopes of being able to apply the strategy clinically. As a result, much is now known concerning its mechanism.5 The protection results from signal transduction pathways emanating from surface receptors. During the preconditioning ischaemia, the receptor agonists bradykinin, opioid, and adenosine are released. The first two bind to Gi-coupled receptors that trigger a complex cascade that involves nitric oxide production and opening of potassium channels in the mitochondria with subsequent redox signalling, which activates an important signalling molecule called protein kinase C (PKC). Adenosine, the third receptor agonist released by ischaemic myocardium, binds to its Gi-coupled receptor, but its signalling bypasses the above … *Corresponding author. Tel: +1 251 460 6812; fax: +1 251 460 6386. E-mail address: mcohen{at}usouthal.edu