Oxidative stress and release of tissue plasminogen activator in isolated rat hearts.
To evaluate the potential of tissue plasminogen activator (t-PA) as a marker of endothelial activation or injury, the dose-response relationship between reactive oxygen intermediates and t-PA release was investigated in isolated rat hearts. After stabilization the hearts were perfused for 10 minutes with different concentrations of hydrogen peroxide (H2O2) (0 (control perfusion), 20, 40, 80, 120, 160, or 200 microM) (n = 8 hearts/group), followed by 30 minutes recovery. Higher concentrations than 80 microM induced cardiac dysfunction and a dose-dependent release of lactate dehydrogenase, indicating myocyte injury. H2O2-concentrations of 80 microM and more caused a significant, but temporary t-PA release. Peak t-PA release occurred more rapidly with higher concentrations, but otherwise there was no difference dependent on the H2O2-dose. The effects of H2O2 (120 or 200 microM) on t-PA release were also compared to the effects of bradykinin. Both were given for 10 minutes as above, and the procedure was repeated after 10 minutes recovery. Bradykinin (50 or 500 nM) released t-PA with the same magnitude, but with peak values occurring earlier than t-PA release induced by H2O2. Bradykinin, but not H2O2, induced t-PA release during the second exposure, suggesting different mechanisms of release.


CONCLUSIONS
Perfusion with H2O2 leads to a dose-dependent myocardial injury in isolated rat hearts. H2O2 also causes an acute t-PA release without dose-dependency, suggesting an all or nothing response of the endothelium. t-PA may be used as an indicator of, but cannot quantify endothelial activation or injury.
Winnerkvist
A
A
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden.
Wiman
B
B
Valen
G
G
Vaage
J
J
D000818:Animals; D006339:Heart Rate; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010958:Plasminogen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left
D010958:Plasminogen; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase