ischaemic preconditioning of the human heart. - Leicester Research ...

4.4 DISCUSSION:
The involvement of K.
%. I-p channels in preconditioning was first suggested by Gross and
Auchampach [ 107] and Auchampach et al 1171 in the canine heart. These authors showed
that channels blockers, glibenclamide and 5-1-113, blocked the protection
induced by
preconditioning and also revealed that apfikalim, a KATP channel opener, mimicked the
cytoprotective effect of preconditioning in reducing infarct size. Subsequently, a plethora
of pharmacological studies have shown that the opening of KATP channels contributes to
the card ioprotect ion of preconditioning in number of models and species including
humans[45,164,165]. However, due to the lack of specific agents modulating the opening
and closing of KATP channels it was not possible at that time to ascertain whether the
beneficial effect of preconditioning was mediated via mitochondrial or sarcolemmal K.. %1-1,
channels or both. Cardiac sarcolemmal KATP channels open in hypoxia to cause
shortening of the action potential. Functionally, the latter is thought to exert an energy-
spafing effect by reducing Ca 2- entry, and until recently sarcolemma K.. %I-p was assumed
to play the major role in card ioprotection by preconditioning [134,3021. However,
cardioprotection can occur under conditions where no action potential shortening can be
detected, arguing against such a mechanism. More recently, Garlid et al [991 showed that
the K.. %. I, p channels opener diazoxide was about 2000-fold more effective in opening
mItoK.. %-rP than sarcoplasmic K' channels in reconstituted bovine heart mitochondria, and
that its card ioprotective potency in rat hearts correlated with its effectiveness on
mitochondrial rather than sarcolemmal channels. Liu et al [ 196] using isolated rabbit
ventricular myocytes used flavoprotein oxidation as an index of mitoK.. %,.,, channel
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