[Limitation of myocardial infarct size by polyethylene glycol-conjugated superoxide dismutase in a canine model of 90 min coronary occlusion followed by 4 days of reperfusion].
The role of oxygen free radicals in the genesis of myocardial reperfusion injury is supported by the studies with superoxide dismutase (SOD) which provides protection against the extention of myocardial injury. However, the efficacy of SOD may be of limited value due to its short plasma half-life of 5-6 min. Conjugation of SOD to polyethylene glycol (PEG-SOD) increases the half-life to greater than 30 hours. Forty-two male, mongrel anesthetized dogs were subjected to occlusion of left circumflex coronary artery for 90 min followed by 4 days of reperfusion. Dogs were randomized to receive either PEG-SOD (1,000 U/kg) or PEG-Albumin via left atrium, starting 15 min before reperfusion and ending simultaneously with reperfusion, and were sacrificed 4 days later. The hearts were stained by ex vivo dual perfusion technique for the determination of myocardial infarct size. Infarct size expressed as a percent of area-at-risk in PEG-SOD (n = 13) and PEG-Albumin (n = 13) treated dogs differed significantly between groups: 29.2 +/- 1.6% vs 44.2 +/- 2.6%, respectively (p less than 0.01) with no observed difference in the size of area-at-risk: 46.0 +/- 1.6% vs 44.4 +/- 1.4% (n.s.). Hemodynamic parameters between groups did not differ during coronary artery occlusion and could not account for the effect of PEG-SOD on infarct size. Collateral blood flows to the inner 2/3 of the ischemic myocardium for both groups did not differ. Plasma SOD activity in PEG-SOD group initially exceeded 20 U/kg and sustained significantly for 4 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Tamura
Y
Y
Saito
S
S
Hatano
M
M
Lucchesi
B R
BR
D000818:Animals; D004285:Dogs; D005609:Free Radicals; D006207:Half-Life; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology; D010100:Oxygen; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase / Q000097:blood / Q000627:therapeutic use*
D005609:Free Radicals; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D010100:Oxygen