Tissue plasminogen activator (t-PA) is a marker of endothelial cell injury or activation. The release of t-PA from isolated rat hearts (Langendorff model) subjected to ischemia-reperfusion or reactive oxygen intermediates (ROI) generated by H2O2 was investigated. H2O2 (200 microM) increased t-PA activity in the coronary effluent to 305 +/- 84% of initial value (mean +/- SEM, p < 0.04 vs controls) at the end of a 10 min intervention. The hydroxyl radical scavenger thiourea (10 mM) only partially inhibited the increase (175 +/- 27%, p < 0.01 compared to controls). 20 min normothermic ischemia increased t-PA activity to 416 +/- 108% (p < 0.005 compared to controls) at the start of reperfusion. In conclusion, cardiac injury by ischemia-reperfusion or ROI increases release of t-PA.