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


CONCLUSIONS
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.
Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan. sonobe@ri.ncvc.go.jp
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Sonobe
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Akiyama
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Shirai
D000818:Animals; D006321:Heart / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors