Protection by nicorandil against the dysfunction of the central vagal baroreflex system following transient global cerebral ischaemia in dogs

Abstract

1 A possible cerebroprotective effect of nicorandil was investigated in a canine model of 5 min global cerebral ischaemia, and compared with protective effects of nitroglycerin and nicardipine. 2 Cerebral ischaemia was produced by occlusion of the left subclavian and the brachiocephalic arteries with preceding ligation of the intercostal arteries. The decrease in baroreflex sensitivity (BRS), measured by phenylephrine-induced reflex bradycardia, was used to assess the cerebroprotective effect. kg-' min-', i.v.) were infused for 60 min just before ischaemia. Nitroglycerin and nicardipine decreased mean arterial blood pressure to an extent similar to that induced by the lower dose of nicorandil. Blood flow in the dorsal medulla oblongata was increased by nicorandil and nicardipine, but not by nitroglycerin. 4 Nicorandil at both doses and nitroglycerin prevented the post-ischaemic decrease in BRS. In these cases, bilateral vagotomy during the reperfusion period decreased BRS, indicating that the vagal component of BRS was protected from ischaemia. On the other hand, nicardipine failed to exert a cerebroprotective effect. 5 The present study suggests that nicorandil may possess a direct cerebroprotective effect and that its property as a nitrate might, at least in part, be important for the observed cerebral protection.

Protective effects of nicorandil against cerebral injury in a swine cardiac arrest model

“…Previous studies have revealed that neuronal cells express 6- to 7-fold more mitoKATPs as the myocardium and it has been demonstrated that mitoKATPs exist in the brain tissue ( 17 , 18 ). Studies assessing the protective effects of nicorandil in the brain have demonstrated that its protective function is mediated by the activation of mitoKATPs ( 19 , 20 ). It has also been determined that premedication with nicorandil induces a cerebroprotective effect in patients receiving liver transplants ( 21 ).…”