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 2030 min of ischaemia. Dialysate 5-HT concentration further increased to 236 +/- 47 nm at 010 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 1030 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.