EFFECTS OF OXYGEN-FREE RADICALS AND SCAVENGERS ON THE CARDIAC EXTRACELLULAR COLLAGEN MATRIX DURING ISCHEMIA-REPERFUSION

OBJECTIVE: Collagen is lysed early during ischemia-reperfusion, but whether this is due to ischemia or reperfusion injury is not known. The effect of oxygen free radical and free radical scavengers on left ventricular hemodynamics, myocardial morphology and collagen content were studied in an isolated, Langendorff-perfused rat heart model of regional ischemia-reperfusion. METHODS: All hearts received left anterior descending coronary artery ischemia for 20 mins. Group 1 had ischemia only; group 2 had ischemia followed by reperfusion with oxygenated Krebs-Henseleit buffer for 20 mins; group 3 had oxygen free radicals generated by hypoxanthine and xanthine oxidase during reperfusion; group 4 had free radical scavengers with superoxide dismutase plus catalase; group 5 had both oxygen free radicals and free radical scavengers during reperfusion. RESULTS: Left ventricular developed pressure decreased significantly in group 3 during ischemia followed by reperfusion (58+/-3.1 mmHg versus 42+/-2.4 mmHg, P=0.004), but did not change significantly in any of the other groups. Necrosis score on pathology was highest in group 3; this score also was higher than that in group 5 with free radical scavengers added (3.0+/-0.3 versus 2.0+/-0.4, P=0.07) and higher than that of group 2 with reperfusion with buffer only (3.0+/-0.3 versus 1.4+/-0.5, P<0.05). Collagen content decreased significantly compared with control in group 3 only with ischemia followed by reperfusion with the addition of oxygen free radicals (18.4+/-1.5 versus 11.9+/-1.7 g/mg protein, P<0.05). The addition of free radical scavengers in group 5 mainly attenuated the collagen loss. Scanning electron microscopy revealed profound structural changes of the extracellular collagen matrix in numerous regions of 'stunning' independent of tissue necrosis. CONCLUSIONS: We conclude that first, oxygen free radicals trigger significant collagen damage and left ventricular dysfunction during reperfusion; second, these changes extend beyond the ischemic damage alone; and third, free radical scavengers can effectively limit oxygen free radical-induced collagen loss and left ventricular dysfunction.