A Geraghty, R Grant, J Stygall, M Sumeray, M Harrison, S Newman, D Yellon & W Pugsley

The Middlesex Hospital and University College London Medical School

Nicorandil is primarily an anti-anginal agent with a relaxatory effect on vascular smooth muscle. It has a dual mode of action as a nitrate and as a potassium channel opener. In addition to its antianginal and cardioprotective activity, Nicorandil has been shown to have cerebroprotective properties. This study was designed to test both the cardioprotective and the neuroprotective properties of Nicorandil in the setting of Coronary Artery Bypass Graft Surgery (CABS).

30 patients with angiographically proven three vessel coronary artery disease and moderate to good left ventricular function (EF>34%) were randomised in a double blind fashion. They received either placebo or Nicorandil 10mg on the evening before surgery and a further 20mg of Nicorandil within 2.5hrs of performing the first coronary artery bypass graft. Each patient underwent a formal neurological examination and neuropsychological assessment, by the battery of ten tests previously described by the Middlesex Hospital Group, within one month of surgery. Repeat testing was carried out 5-7 weeks after surgery. A standardised anaesthetic protocol was used and surgery was carried out on cardiopulmonary bypass by a single surgeon (WP) using intermittent cross clamp fibrillation. Transcranial Doppler (EME) was used to assess microembolic load and measure middle cerebral artery blood flow velocity. ATP levels were measured in myocardial biopsies taken before cross-clamping the aorta, after 10 minutes of ischaemia and after 10 minutes of reperfusion. Blood samples for Troponin T levels were taken before CPB, 1hr, 6hrs,24hrs and 72hrs after CPB

Results: There was no significant difference in the incidence of neuropsychological deficit between the nicorandil treated group and the control group; changes in ATP levels and Troponin T release were similar in the two groups.

Conclusion: A drug with promising cerebro and myocardial protective properties on preclinical testing has failed to show any clinically apparent protection when given to patients undergoing routine CABG surgery.