Wael I Awad, Michael J Shattock, David J Chambers.

Cardiovascular Research, The Rayne Institutr, St Thomas’ Hospital, London

The role of the K ATP channel in ischaemic preconditioning (IP) in the adult rat heart is controversial. This study investigates whether IP protection induce by 3 min ischaemia : 3 min reperfusion, 5 min ischaemia : 5 min reperfusion protocol was abolished by glibenclamide (G), a widely used but non-specific KATP channel blocker or 5-hydroxy decanoic acid (5HD), a specific KATP channel blocker. Adult rat hearts (n=6/group) were Langendorff perfused for 20 min to equilibrate and then pretreated with G or 5HD before the IP protocol. Hearts were then subjected to 35 min global ischaemia and 60 min reperfusion. Recovery of LVDP (measured with an intra-ventricular balloon) was expressed as percent baseline value at 20 min. Preconditioning protection (62+6%) was abolished by 20 min pretreatment with G (10m M) or 5HD (m M) (43+4% and 23+5% recovery respectively); 5 min pretreatment was insufficent. Having established that KATP channel may play a role in preconditioning in the adult rat heart, we hypothesised that the previously described inability of the neonate to be preconditioned (and its increased tolerance to ischaemia) may reflect endogenous upregulation of the mechanisms responsible for preconditioning; thus KATP channel blockade should exacerbate ischaemic injury in the neonate. Neonatal (4-6 day old) rat hearts (n=6/group) were pretreated for 30 min with 5HD (50m M) before 45 min global ischaemia and 60 min reperfusion. This KATP channel blocker had no effect on tolerance to ischaemia (recovery 39+3% in 5HD vs 45+5% in controls). We conclude that preconditioning in the adult rat heart can be abolished by blocking KATP channels; however, pre-existing preconditioning does not appear to underlie neonatal ischaemic tolerance or the inability of the neonatal heart to be further protected by preconditioning.