Contribution of serotonin uptake and degradation to myocardial interstitial serotonin levels during ischaemia-reperfusion in rabbits

Aim Although deleterious effects of serotonin (5‐HT) have been demonstrated during myocardial ischaemia‐reperfusion, little information is available on myocardial interstitial 5‐HT kinetics. This study evaluated the contribution of 5‐HT reuptake and degradation to myocardial interstitial 5‐HT levels during ischaemia‐reperfusion. Methods Using microdialysis technique in anaesthetized rabbits, we monitored myocardial interstitial 5‐HT levels in the ischaemic region during ischaemia (30 min) followed by reperfusion (60 min) and investigated the effects of local infusion of fluoxetine, a 5‐HT uptake inhibitor, and/or pargyline, a monoamine oxidase inhibitor. Results In vehicle control, dialysate 5‐HT concentration increased gradually from 16 ± 3 at baseline to 85 ± 18 nm during 20–30 min of ischaemia. Dialysate 5‐HT concentration further increased to 236 ± 47 nm at 0–10 min of reperfusion and then began to decline. Averaged 5‐HT concentration was 61 ± 11 during ischaemia and 113 ± 13 nm during reperfusion. Fluoxetine elevated dialysate 5‐HT level at baseline and at 10–30 min of reperfusion; it increased averaged dialysate 5‐HT concentration by approx. 304% during reperfusion compared to control. Pargyline elevated averaged dialysate 5‐HT concentration during ischaemia by approx. 243% and that during reperfusion by approx. 250% compared to control. The changes in dialysate 5‐HT concentration by fluoxetine + pargyline were similar to those of fluoxetine alone. Conclusion The 5‐HT reuptake function plays an important role in the clearance of myocardial interstitial 5‐HT during reperfusion. When 5‐HT reuptake function is intact, degradation of 5‐HT by monoamine oxidase contributes to reduce myocardial interstitial 5‐HT level throughout ischaemia‐reperfusion.