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 radicals 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.
Lonn
E
E
Centre for Cardiovascular Research, University of Toronto, Ontario.
Factor
S M
SM
Van Hoeven
K H
KH
Wen
W H
WH
Zhao
M
M
Dawood
F
F
Liu
P
P
D000818:Animals; D002374:Catalase / Q000494:pharmacology*; D003094:Collagen / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005109:Extracellular Matrix / Q000187:drug effects*; D016166:Free Radical Scavengers; D005609:Free Radicals; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008855:Microscopy, Electron, Scanning; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000494:pharmacology*
D016166:Free Radical Scavengers; D005609:Free Radicals; D007042:Hypoxanthines; D017382:Reactive Oxygen Species; D019271:Hypoxanthine; D003094:Collagen; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase