## 4 Discussion
In humans, this increase in plasma 5-HT could also be observed: [PERSON] et al. studied 30 cases of AMI and compared them with 13 cases of unstable angina. They reported a rapid increase in plasma 5-HT within the first 24 h after AMI, compared to no alteration in the unstable angina group. Moreover, they found an association between the severity of AMI and plasma 5-HT levels [25]. As discussed by [PERSON] and [PERSON] [38] and as we experienced in previous experiments, the accurate generation of plasma for the determination of 5-HT levels is delicate and easily prone to error. Plasma concentrations of 5-HT are very low under physiologic conditions [13] and any activation of platelets during the process of plasma generation needs to be strictly avoided. To ensure that, immediate and gentle processing of blood samples is necessary, which is not always possible in clinical practice. We therefore aimed to evaluate serum 5-HT as a potential biomarker, which is much easier to handle and less prone to error. However, we could neither find differences in serum serotonin levels between our STEMI cohort and the control group nor find any changes in 5-HT levels detectable within the 24 h study period in our collective. A second objective of our pilot study was to examine whether serum 5-HT was suitable as a biomarker for I/R injury. As mentioned above, early reperfusion is mandatory in patients with STEMI to salvage myocardium and reduce infarct size. However, reperfusion itself might provoke additional injury, leading to increased infarct size and microvascular dysfunction [10; 39]. This deleterious process of reperfusion is characterized by ionic imbalance [40; 41; 42] and excess formation of reactive oxygen species [41], both contributing to necrosis, apoptosis, and cell death [10]. All these processes lead to impaired myocardial blood flow, resulting in the no-reflow phenomenon, myocardial stunning, and reperfusion arrhythmias [10]. About 35% of STEMI patients suffer from incomplete reperfusion due to severe I/R injury [43]. Currently, myocardial damage induced by I/R injury cannot be monitored due to a current lack of specific biomarkers. It is well established that 5-HT causes deleterious effects in I/R injury: In 1994, it was first demonstrated that administration of nexopamil, a combined Ca\({}^{2+}\) and 5-HT antagonist, reduced myocardial damage in a pig model after LAD occlusion [44]. In 2014, [PERSON] et al. showed that the administration of fluoxetine, a selective 5-HT reuptake inhibitor, prevented I/R injury after aortic surgery in rats [45]. It was claimed that 5-HT deteriorates I/R injury by enhancing oxidative stress caused by mitochondrial monoaminooxidase-A (MAO-A) activity during the process of 5-HT degradation [46]. [PERSON] et al. recently found that 5-HT aggravates myocardial I/R injury by aggravating neutrophil degranulation, and that I/R injury was accompanied by an elevation in 5-HT plasma levels [12]. Moreover, when _Tph1-/-_ mice (mice without peripheral serotonin) were subjected to myocardial ischemia with reperfusion, the infarct size was significantly reduced by about 35% compared to wildtype (WT) controls [12]. We therefore hypothesized that serum 5-HT levels might be associated with I/R injury in our collective. We used the comparison of ST-segment elevation in standard 12-lead ECG prior to and after PCI as a surrogate marker for I/R injury. Incomplete resolution of ST-segment elevation has been shown to be an indicator for I/R injury and a prognostic marker for 90-day prognosis, death, development of heart failure, and shock [30; 31]. Moreover, we additionally analyzed the visual markers TMP and MGB for the assessment of I/R injury: Impaired perfusion of the myocardium in coronary arteriography assessed by use of the TMP grade was described to be related to a higher risk of mortality [47]. Moreover,the outcome assessed by the MBG was also associated with mortality in patients with STEMI [34]. Contrary to our expectations, 5-HT serum levels did not correlate with I/R injury in our collective.