EFFECTS OF NICORANDIL AND GLYCERYL TRINITRATE ON INFARCT SIZE, ADENOSINE RELEASE, AND NEUTROPHIL INFILTRATION IN THE DOG

Objective: The major aim of this study was to determine if nicorandil, a potassium channel opener nitrate, produces a reduction in myocardia l infarct size at a non-hypotensive dose in dogs and to determine if t his effect is the result of an increase in adenosine release or reduct ion in neutrophil infiltration into the ischaemic area. Glyceryl trini trate was used for purposes of comparison. Methods: Barbitone anaesthe tised dogs were subjected to 60 min of left anterior descending corona ry artery occlusion followed by 3 h of reperfusion. Nicorandil (100 mu g . kg(-1) bolus followed by a 10 mu g . kg(-1). min(-1) infusion; NC /pre group), glyceryl trinitrate (10 mu g . kg(-1) bolus followed by a 1 mu g . kg(-1). min(-1) infusion; GTN/pre group), or an equivalent v olume of saline (control group) were given intravenously 15 min before occlusion and continued to the time of reperfusion. In two other grou ps, nicorandil (NC/post group) or glyceryl trinitrate (GTN/post group) were given IO min before reperfusion and continued until the end of t he experiment. To measure the release of adenosine from the ischaemic region, coronary venous blood samples were collected before occlusion, during occlusion, and at various times following reperfusion. Myocard ial infarct size was determined by triphenyltetrazolium chloride and t ransmural myocardial blood flow by radioactive microspheres. Transmura l myeloperoxidase activity, an index of neutrophil infiltration, was m easured in biopsies obtained from the area at risk. Results: Pretreatm ent with nicorandil and glyceryl trinitrate caused a marked reduction in myocardial infarct size expressed as percent of the area at risk [N C/pre group, 7.8(SEM 1.6)%; GTN/pre group, 11.9(2.3)%; control group, 31.0(5.6)%]. When nicorandil and glyceryl trinitrate were given before reperfusion, both drugs still produced a significant reduction in inf arct size [NC/post group, 13.8(2.0)%; GTN/post group, 18.9(4.3)%]. Cor onary venous adenosine concentrations during reperfusion were signific antly lower in both nicorandil and glyceryl trinitrate pretreated grou ps, but not in the post-treated groups. Transmural myeloperoxidase act ivity was significantly lower in both nicorandil treated groups. Concl usions: Pretreatment with a non-hypotensive dose of nicorandil or glyc eryl trinitrate markedly reduces myocardial infarct size and adenosine release from the ischaemic-reperfused area. These agents were also ef fective, but to a lesser degree, when given just before reperfusion. T he cardioprotective actions of nicorandil appear to be related not onl y to its potassium channel opening activity but also in part to its ni trate activity.