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

Figure 4.7 shows that ischaemia alone resulted in a significant increase in CK leakage
and that preconditioning completely reversed the effect of ischaernia so that CK leakage
was similar to that seen in the aerobic control group. It also shows that glibenclamide ( 10
pM), which blocks K...,
-I-p channels both in the sarcolemma and the mitochondrial inner
membrane, partially blocked the beneficial effect of preconditioning on
CK leakage
5-HD is a K.. %-p channel blocker which appears to show selectivity for mitoK, %,.,, channels
over sarcolemmal KAýI-p.
Thus 5-HD has been shown to block K.. %. I-p channels in isolated mitochondria 11451 but did
not affect sarcolemmal K.. kj-p currents activated by cromakahm 12071. In isolated rabbit
cardiac myocytes, Sato et al 12661 have recently shown that 5-HD inhibited oxidation in
response to the opener pinacidil, but did not block sarcolemmal K. ý-j 1, current activated by
the same opener, consistent with 5-HD showing selectivity for blocking of mitoK. ý 11, over
sarcolemmal
Figure 4.7 also shows that 5-HD (I mM) abolished the protective
effect of PC on CK leakage in human myocardium We also used the novel
sulphonylthiourea IIMR 1883, which is thought to have the reciprocal selectivity to 5-
HD, preferentially blocking the sarcolemmal K. %., -,, channel j 102,1901. HMR 1883 did not
block the protective effect of preconditioning.
The results in Figure 4.7 also show the effects of pretreatment with K: xl-p channel openers
in the absence of an ischemic preconditioning stimulus. Both the non-selective K..
xri,
channel opener pinacidil and the selective opener of mitoK: %, -,. channels diazoxide were
protective, with diazoxide reducing CK leakage to levels not significantly
different from
those obtained with PC itself and pinacidil exhibiting a less potent efflact than PC. In this
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