Superoxide dismutase decreases reperfusion arrhythmias and preserves myocardial function during thrombolysis with tissue plasminogen activator.
Release of superoxide radicals during the early phase of coronary reperfusion may result in degradation of endothelium-derived relaxing factor (EDRF), extension of myocardial injury, precipitation of arrhythmias, and stimulation of platelet aggregation. These factors may relate to the occurrence of ventricular fibrillation during reperfusion and coronary reocclusion following initial thrombolysis. This study was designed to examine the effects of concomitant administration of superoxide radical scavenger superoxide dismutase (SOD) with tissue plasminogen activator (tPA) compared to tPA alone (without SOD) in acute coronary thrombosis in anesthetized dogs. Dogs with a stable electrically induced coronary thrombus were randomly given intravenously tPA (0.75 mg/kg) alone or SOD bolus (2 mg/kg) followed by SOD (4 mg/kg) + tPA (0.75 mg/kg) over 20 min. tPA alone restored coronary blood flow in six of nine dogs (reperfusion rate of 67%) with time to reflow of 18.5 +/- 6.7 (mean +/- SD) min. Coronary reocclusion occurred spontaneously in four of six dogs with initial reperfusion (reocclusion rate of 67%). In contrast, SOD + tPA restored coronary blood flow in 9 of 12 dogs (reperfusion rate of 75%, not significant vs. tPA alone) with time to reflow of 11.3 +/- 4.8 min and coronary reocclusion occurred in only 3 of 9 dogs with reperfusion (reocclusion rate of 33%, not significant vs. tPA alone). Reperfusion arrhythmias were more frequent in dogs who received tPA alone compared to those who received SOD in addition to tPA (mean Holter-monitored PVC count of 730 vs. 12 beats/h, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Mehta
J L
JL
Department of Medicine, University of Florida College of Medicine, Gainesville.
Nichols
W W
WW
Saldeen
T G
TG
Chandna
V K
VK
Nicolini
F A
FA
Lawson
D L
DL
ter Riet
M F
MF
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003327:Coronary Disease / Q000188:drug therapy*; D003328:Coronary Thrombosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D015425:Myocardial Reperfusion; D010974:Platelet Aggregation / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use*
D011994:Recombinant Proteins; D013482:Superoxide Dismutase; D010959:Tissue Plasminogen Activator; D000109:Acetylcholine