Cardiac oxidase systems mediate oxygen metabolite reperfusion injury.
To investigate the mechanism of cardiac ischemia reperfusion injury, we fed rats tungsten (3 weeks) to inhibit molybdenum-dependent oxidase enzymes. Tungsten-treated isolated perfusion hearts (Langendorff, ventricular balloon, 37 degrees C) had negligible xanthine oxidase activity (less than 0.3 vs greater than 8.0 U/gm myocardium) and improved recovery of developed pressure (DP), contractility (+dP/dt), and compliance (-dP/dt) after 20 minutes of global ischemia (37 degrees C) and 40 minutes of reperfusion. Furthermore, the addition of dimethylthiourea, a freely diffusible O2 metabolite scavenger, but not equimolar urea, a non-O2 metabolite scavenger, improved recovery. High-dose urea improved recovery more than control but less than dimethylthiourea. Combining tungsten and equimolar urea improved recovery the same as dimethylthiourea. We conclude that: (1) inhibition of myocardial oxidase enzymes (including xanthine oxidase) improves recovery of ventricular function after ischemia and reperfusion in the isolated rat heart, (2) infusion (during reperfusion) of a permeable O2 metabolite scavenger (dimethylthiourea) but not equimolar urea improves recovery of ventricular function, (3) infusion of higher concentrations of urea improves postischemic function, and (4) myocardial reperfusion injury is distinguishable from ischemic injury.
D000818:Animals; D004032:Diet; D006321:Heart / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013318:Stroke Volume; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014414:Tungsten / Q000008:administration & dosage / Q000494:pharmacology; D014508:Urea / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
C038983:1,3-dimethylthiourea; D014508:Urea; D014969:Xanthine Oxidase; D013890:Thiourea; D014414:Tungsten