OBJECTIVE
To assess the effect of nicorandil on serum concentration of nitrogen oxides, participants and modulators of NO-synthase reactions and interrelated participants of transmethylation in 2 hours after administration, as well as to analyze early postoperative outcomes of arterial reconstructions in patients with coronary artery disease (CAD).
MATERIAL AND METHODS
The study included 60 patients with class II-III angina pectoris who underwent femoropopliteal bypass surgery. All patients were randomized into two equal groups: control group (n=30) and main group (n=30). In the last group, nicorandil (Cordinic, PIQ-Pharma) was prescribed 2 hours before surgery in addition to basic therapy with a maximum single dose of 20 mg. Blood samples were taken before and 2 hours after taking pills, as well as immediately before sedation. The main goal was to determine the concentration of nitrogen oxides, participants and modulators of NO-synthase reactions (arginine and citrulline) and interrelated participants in transmethylation (total homocysteine and methionine). We assessed the incidence and structure of cardiovascular complications (CVC) in postoperative period.
RESULTS
Both groups were comparable by clinical characteristics, drug therapy and duration of arterial reconstruction. There were no significant changes in serum concentration of total nitrogen oxides according to metabolic analysis in 2 hours after nicorandil taking. We observed an increase in the content of arginine (Arg) as a substrate of NO-synthase reactions (p=0.018), decrease of citrulline (Cyt) as a product of these reactions (p=0.038) and increase of Arg/Cyt ratio (p=0.00037). The levels of total homocysteine, methionine and their ratios were not significantly changed. We found significant between-group difference in myocardial injury. In the control group, high-sensitivity cardiac troponin was increased in 24 hours after surgery in 5 cases that indicated intraoperative myocardial damage. At the same time, no increase of troponin was observed in the main group (16.7% vs. 0%, p=0.002). Incidence of early postoperative CVC (myocardial infarction and injury, rhythm disturbances, heart failure, stroke) was significantly less in the main group (6.7% vs. 33.3%, p=0.001).
CONCLUSION
No significant changes in serum concentration of nitrogen oxides after taking nicorandil indicate its direct exposure without indirect conversion to nitric oxide. Direct effect on K-transporter activates intracellular metabolic functions including increase of Arg/Cyt ratio. Probably, it happens due to resynthesis of Arg from Cyt in tissues that contributes to increase of Arg pool and, accordingly, bioavailability of substrate for NO-synthase reactions. Application of nicorandil (Cordinic, PIQ-Pharma) before vascular interventions reduces the incidence of CVC in early postoperative period.
