EFFECT OF NICORANDIL ON POST‐ISCHAEMIC CONTRACTILE DYSFUNCTION IN THE HEART: ROLES OF ITS ATP‐SENSITIVE K’ CHANNEL OPENING PROPERTY AND NITRATE PROPERTY

Abstract

1. This study aimed to characterize the effect of nicorandil (NC) on myocardial stunning and the role of ATP-sensitive K+ (KATP) channel opening property in its cardioprotective action. 2. In open-chest anaesthetized rabbits, myocardial stunning was induced by 10 min of coronary occlusion followed by 30 min of reperfusion. As an index of regional contractile function, systolic thickening fraction (TF) was measured by an epicardial Doppler sensor. The doses of NC (10 micrograms/kg per min) and nitroglycerin (TNG) (1 micrograms/kg per min) were selected not to lower the systemic blood pressure significantly. 3. In the untreated controls, TF at 30 min after reperfusion was 46.4 +/- 2.9% of the baseline value, indicating myocardial stunning. Both NC and TNG significantly improved post-ischaemic recovery of TF when administered during the pre-ischaemic and post-ischaemic periods (TF = 68.2 +/- 6.4%, 64.7 +/- 2.3%, respectively). However, when their infusion was restricted to a pre-ischaemic 10 min period, TF recovery was improved by NC, but not by TNG (63.4 +/- 7.9%, 40.9 +/- 6.2%, respectively). 4. Pretreatment with glibenclamide (GL; 0.3 mg/kg) did not influence the recovery of TF after the 10 min ischaemia (TF = 52.4 +/- 3.9% at 30 min after reperfusion). However, after the GL injection, a cardioprotective effect from nicorandil pretreatment was not detected (TF = 51.3 +/- 1.7%). 5. These results suggest that nicorandil protects the myocardium against stunning by opening the KATP channel when it is given before ischaemia, and that the nitrate property of nicorandil may also play a role during the reperfusion period in attenuation of post-ischaemic contractile dysfunction.