The potential cardioprotective effect of two pure
potassium channel openers,
bimakalim (
EMD 52692) and
aprikalim (
RP 52891), on myocardial ischaemia/
reperfusion injury was investigated in
barbital-anaesthetized dogs. In a model of reversible ischaemia/
reperfusion injury, administration of
bimakalim as an intravenous bolus prior to ischaemia or administration of a non-hypotensive dose of
aprikalim as a constant
intravenous infusion resulted in a reduction in reperfusion contractile dysfunction (
myocardial 'stunning') produced by a single 15-min coronary artery occlusion. Administration of
aprikalim only during the reperfusion period had no beneficial effect. Similarly, in a model of irreversible ischaemia/
reperfusion injury (90 min of coronary artery occlusion followed by 5 h of reperfusion),
intravenous infusion of
bimakalim at a dose which reduced aortic blood pressure approximately 15-20 mmHg or infusion of
aprikalim at a non-hypotensive dose throughout the entire experiment produced a significant reduction in
myocardial infarct size. A protective effect of
bimakalim was not observed when it was administered during the reperfusion period only. In both the
stunned myocardium model as well as the infarcted myocardium model, the beneficial effects of the
potassium channel openers could not be attributed to differences in the traditional determinants of the extent of ischaemia/
reperfusion injury; area at risk size, oxygen consumption, or collateral blood flow. Furthermore, the anti-ischaemic actions of the
potassium channel openers were blocked by pre-treatment with the
ATP-dependent
potassium (
KATP) channel antagonist,
glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS)