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 wh ether this is due to ischemia or reperfusion injury is not known. The effect of oxygen free radical and free radical scavengers on left vent ricular hemodynamics, myocardial morphology and collagen content were studied in an isolated, Langendorff-perfused rat heart model of region al ischemia-reperfusion. METHODS: All hearts received left anterior de scending coronary artery ischemia for 20 mins. Group 1 had ischemia on ly; group 2 had ischemia followed by reperfusion with oxygenated Krebs -Henseleit buffer for 20 mins; group 3 had oxygen free radicals genera ted by hypoxanthine and xanthine oxidase during reperfusion; group 4 h ad free radical scavengers with superoxide dismutase plus catalase; gr oup 5 had both oxygen free radicals and free radical scavengers during reperfusion. RESULTS: Left ventricular developed pressure decreased s ignificantly in group 3 during ischemia followed by reperfusion (58+/- 3.1 mmHg versus 42+/-2.4 mmHg, P=0.004), but did not change significan tly in any of the other groups. Necrosis score on pathology was highes t in group 3; this score also was higher than that in group 5 with fre e radical scavengers added (3.0+/-0.3 versus 2.0+/-0.4, P=0.07) and hi gher 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 c ompared with control in group 3 only with ischemia followed by reperfu sion 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 micr oscopy revealed profound structural changes of the extracellular colla gen matrix in numerous regions of 'stunning' independent of tissue nec rosis. CONCLUSIONS: We conclude that first, oxygen free radicals trigg er 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.