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

It should be mentioned that the preparation used in this study was not electrically
stimulated (i. e. non-beating) and therefore one should be cautious when extrapolating to
the in Ovo situation.
It should also be emphasized, that in common with previous studies in non-human
hearts [99,196,2661, my evidence for the involvement of mitoK.. %.,,, rather than
sarcolernmal Kx-,
ý,, channels depends strongly on the selectivity of the K\11, channel
openers and blockers used, in particular diazoxide, 5-1-113,
and HMR1883 In this
context, the concentration of diazoxide that I used (100 [M) has been reported to activate
mitoK. but
N-1-1, not sarcolemmal K.,
%-I-p in rabbit ventricular myocytes [ 1961. HMR 1883
should be an effective blocker of sarcolemmal K..
\., 1, channels at 10 pM, since its reported
K, for these channels is 0.8 4M [1021, though its effects on mitoK..
xll, have not been
tested directly. 5-HD is an effective blocker of mitoK. %j-p provided that the channel is
opened by a physiological or pharmacological opener [145,1961, but its selectivity for
mitoK., \, I-p over sarcolemmal K..
%. I-p merits further study. Notsu et a] [2321 reported block
of sarcolemmal K. x-j-p channels in guinea pig myocytes by 5-HD, though more recently
Hu et al [137] have argued that 5-HD at a concentration of 0.5 mM selectively blocks
mItoK.. ý-j-j, without affecting sarcolernmal KATP channels of rabbit ventricular cells.
Certainly, 5-HD at a concentration of I mM was an effective blocker of card ioprotect ion
in this human model.
In conclusion, the present study provides strong evidence that mitochondrial rather
than sarcolemmal K,.
%. I-p channels are effectors of Ischaernic preconditioning in the human
myocardium. The finding has obvious important clinical implications, however, the
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