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.