TAURINE PROTECTS THE HEART FROM NEUTROPHIL-INDUCED REPERFUSION INJURY

Deficiency of the amino acid taurine is implicated in various patholog ic states of the heart. Besides other effects, taurine has been propos ed to be an antioxidant. However, its benefit under conditions associa ted with the generation of reactive oxygen species in the heart has no t been clearly demonstrated. To assess the potential of taurine to inf luence neutrophil-dependent reperfusion injury, a model was developed based on the isolated working guinea pig heart. After an initial work phase, hearts were subjected to 15 min of global ischemia. Reperfusion , in a nonworking mode, was carried out in the absence or presence of homologous neutrophils (PMN) and/or taurine. After 15 min, work was re sumed and percentage recovery of function was determined another 20 mi n later. During the reperfusion phase, coronary venous effluent was co llected to quantify release of lactate and glutathione, markers of isc hemic challenge and redox-stress, respectively. Furthermore, direct ef fects of taurine on radical formation were investigated in a chemilumi nescence assay. Control hearts without application of PMN or taurine h ad a postischemic recovery of external heart work (EHW) of 76%, in the presence of taurine (15 mM) recovery was 72%. The application of PMN for merely the first minute of reperfusion led to a significant decrea se in recovery to 30%, PMN having no effect without a foregoing ischem ia. When taurine was additionally applied during reperfusion, EHW reco vered to 60%. Release of lactate and of oxidized glutathione (GSSG) di d not differ between the groups. In contrast, effluent concentrations of reduced glutathione (GSH) were considerably elevated by the presenc e of PMN in the sample and remained high even after PMN-washout Taurin e tended to attenuate this PMN effect. At the 5th and 10th min of repe rfusion, GSH release of individual hearts correlated inversely with po stischemic recovery of EHW. Surprisingly, taurine, by itself, did not significantly alter glutathione release. However, taurine (15 mM) mark edly reduced luminol-dependent chemiluminescence elicited by activated guinea pig PMN as well as by chemically generated hypochlorous acid a nd hydroxyl radicals, but not superoxide radicals. Our results demonst rate that taurine protects the heart from PMN-induced reperfusion inju ry and oxidative stress. Because respiratory burst activity of PMN was also significantly reduced in the presence of taurine, the beneficial effect appears to be mediated by antioxidative properties of taurine.