Aims The increased tolerance to myocardial ischaemia observed during the se
cond of two sequential exercise tests, i.e. the warm-up phenomenon, has bee
n proposed as a clinical model of ischaemic preconditioning. As ATP-sensiti
ve K+ channels appear to be a mediator of ischaemic preconditioning in both
experimental and clinical studies, the aim of this study was to investigat
e the role of K-ATP channels in the warm-up phenomenon.
Methods and Results Twenty-six patients with coronary artery disease were r
andomized to receive 10 mg oral glibenclamide, a selective ATP-sensitive K channel blocker. or placebo. Sixty minutes after glibenclamide or placebo
administration, patients were given an infusion of 10% dextrose (8 ml . min
(-1)) to correct glucose plasma levels or, respectively, an infusion of sal
ine at the same infusion rate. Thirty minutes after the beginning of the in
fusions, both patient groups underwent two consecutive treadmill exercise t
ests, with a recovery period of 15 min to re-establish baseline conditions.
Before exercise tests, blood glucose were similar in placebo and glibencla
mide groups (96 +/- 10 vs 105 +/- 22 mg . 100 ml(-1), P = ns). After placeb
o administration, rate-pressure product at 1.5 mm ST-segment depression sig
nificantly increased during the second exercise test compared to the first
(220 +/- 41 vs 186 +/- 29 beats . min(-1) . mmHg . 10(2), P<0.01), but it d
id not change after glibenclamide (191 +/- 34 vs 187 +/- 42 beats . min(-1)
. mmHg . 10(2), P = ns), with a significant drug-test interaction (P=0.009
1, at two-way ANOVA).
Conclusions Glibenclamide, at a dose previously shown to abolish ischaemic
preconditioning during coronary angioplasty, prevents the increase of ischa
emic threshold observed during the second of two sequential exercise tests.
These findings confirm that ischaemic preconditioning plays a key role in
the warm-up phenomenon and that in this setting is, at least partially, med
iated by activation of ATP-sensitive K+ channels.