Effects of serotonin transporters on myocardial cell injury during ischemia/reperfusion in rats

Figures

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  Fig. 1. Schematic illustration of the cardiac microdialysis technique. The dialysis probe is placed in the left coronary artery-perfused area of the left ventricular wall. When a drug (fluoxetine or decynium 22) is locally administered to the myocardial interstitium via the probe, myoglobin released due to myocardial cell injury is simultaneously collected in the dialysate.

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  Fig. 2. Illustration of experimental protocol. After 15-min baseline dialysate sampling, 15-min dialysate samples were collected during the ischemia period of 30 min followed by reperfusion period of 30 min. In the control group, the dialysis probe was continuously perfused with Ringer's solution throughout the experiment. In the drug-treated groups, the dialysis probe was perfused with Ringer's solution for the first hour, followed by the drug solution for one hour prior to the first sampling.

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  Fig. 3. Dialysate myoglobin concentrations during myocardial ischemia/reperfusion in control, fluoxetine-treated, decynium 22-treated, and co-treated groups. *P < 0.05; **P < 0.01; ‡P < 0.01 vs. baseline; #P < 0.01 vs. 0–15 min of ischemia; §P < 0.01 vs. 15–30 min of ischemia; ‖P < 0.05 and ¶P < 0.01 vs. 0–15 min of reperfusion.

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  Fig. 4. Mechanism of serotonin transporter regulation in myocardial ischemia/reperfusion injury in control rat. During myocardial ischemia/reperfusion, 5-HT released from activated platelets is partially reuptaken via platelet serotonin reuptake transporter (SERT), suppressing excessive 5-HT accumulation. Plasma membrane monoamine transporter (PMAT) mediates 5-HT uptake into cardiomyocytes. Monoamine oxidase (MAO) degrades 5-HT in cardiomyocytes, producing hydrogen peroxide (H2O2).

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  Fig. 5. Mechanism of serotonin transporter regulation in myocardial ischemia/reperfusion injury in fluoxetine-treated rat. Serotonin reuptake transporter (SERT) inhibition nullifies the platelet reuptake mechanism, resulting in marked 5-HT accumulation. Excessive 5-HT causes vasoconstriction and platelet aggregation through receptors, leading to microcirculatory disturbance and reduced oxygen supply. Because plasma membrane monoamine transporter (PMAT)-mediated uptake into cardiomyocytes is maintained, SERT inhibition by fluoxetine may exacerbate myocardial cell injury in the ischemic period and dramatically increase myoglobin release during early reperfusion (0–15 min of reperfusion). MAO, monoamine oxidase; H2O2, hydrogen peroxide.

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  Fig. 6. Mechanism of serotonin transporter regulation in myocardial ischemia/reperfusion injury in decynium 22-treated rat. Plasma membrane monoamine transporter (PMAT) inhibition blocks 5-HT uptake into cardiomyocytes, but reuptake via platelet serotonin reuptake transporter (SERT) is maintained, preventing excessive 5-HT accumulation. Myoglobin efflux is similar to that of the control group, suggesting that the effect of 5-HT reuptake into cardiomyocytes on myocardial ischemia/reperfusion injury is weaker than that of SERT-mediated platelet 5-HT reuptake.