Abstract 16460: Serotonin Influences Inflammatory Cell Recruitment During Myocardial Ischemia-Reperfusion Injury in Mice
Introduction: Cardiac tissue serotonin levels are increased in myocardial infarction. The role of serotonin in ischemia-reperfusion (I/R) injury however is not well understood. Tryptophan hydroxylase-1-deficient mice (Tph1-/-) lack peripheral serotonin. Investigating these mice we found recently that platelet serotonin promotes inflammatory cell recruitment.
Hypothesis: Serotonin may regulate inflammatory cell recruitment during myocardial I/R injury.
Methods: Twelve week-old C57Bl/6 (WT) and Tph1-/- mice where subjected to a 30 minute ligation of the left anterior descending coronary artery. Reperfusion was allowed for 24 hours. Infarct size was determined by double staining with monolite blue/triphenyl tetrazolium chloride and in echocardiography. Hearts of non-operated mice were excised and perfused in working mode using Krebs-Henseleit buffer containing 0.4 mM palmitate and 5 mM glucose in the absence of blood cells. In addition, working hearts were subjected to 20 minutes of global no-flow ischemia with subsequent reperfusion for 25 minutes.
Results: Serum troponin increased after I/R injury compared to sham-operated mice. Myocardial I/R injury was attenuated in living Tph1-/- mice: Mean infarct size was 53.5±13% of myocardium at risk in WT and 36.9±10% in Tph1-/- mice (n=8; p<0.05). In isolated working hearts cardiac power (30.7±3 versus 32.9±4 mW/gHW; n.s.) and developed aortic pressure (24.1±3 versus 23.6±2 mmHg; n.s.) were similar. Isolated working hearts subjected to no-flow ischemia failed gradually, but recovered similarly in both groups after reperfusion. Infiltration of infarcted myocardium with platelet-binding neutrophils (platelet-neutrophil complexes - PNC) was reduced in Tph1-/- mice in histology and flow cytometry.
Conclusion: Lack of non-neuronal serotonin decreased tissue damage after myocardial I/R injury in vivo. Isolated, i.e. denervated and blood cell-deprived hearts from Tph1-/- mice were equally susceptible to global I/R injury as hearts from WT mice, suggesting that this depended on blood cells. PNC invasion into infarcted myocardium was reduced in Tph1-/- mice. In conclusion, blood-derived serotonin regulates inflammatory cell recruitment during myocardial I/R injury.
- © 2013 by American Heart Association, Inc.