Effects of polyoxyethylene-modified superoxide dismutase on reperfusion induced arrhythmias in isolated rat and guinea-pig hearts.
Effects of a newly introduced polyoxyethylene-modified superoxide dismutase (SOD-POE) with prolonged plasma half life (10 h) on reperfusion induced arrhythmias were examined using a 15 min left anterior descending coronary artery (LAD) occlusion followed by reperfusion in the isolated perfused rat and guinea-pig hearts. LAD occlusion was performed by compressing the artery using a suction cup placed on the LAD to which negative pressure was applied. The LAD occlusion was repeated twice at an interval of 20 min. Drugs were infused from 10 min prior to the occlusion to 3 min after reperfusion at either first or second trial of the occlusion and release. ECG was monitored throughout the experiments. In the control group (rat hearts), arrhythmias including ventricular fibrillation (Vf) (incidence, 64.3 to 83.3%), ventricular tachycardia (VT) (66.7 to 84.6%), premature ventricular contraction (PVC) and premature atrial contraction (PAC) occurred immediately after reperfusion and lasted for 1 to 3 min. In both groups treated with SOD-POE (10 U/ml) or native human SOD (10 U/ml), the incidence of Vf and VT was 0% and the number of PVCs significantly decreased. Lidocaine (5 x 10(-7) M, 10(-6) M) also reduced the incidence of VT and the number of PVCs. In guinea-pig hearts, the occlusion and release induced Vf (50%), VT (80%), PVCs and PACs. Both SOD-POE and SOD markedly depressed the incidence of Vf (0%) and VT (14.3% in both groups) and decreased the number of PVCs and PACs. Results demonstrate that SOD-POE has the same pharmacological activity as SOD does in preventing reperfusion induced arrhythmias in isolated rat and guinea-pig hearts, suggesting that it will provide a novel therapeutic approach for preventing oxygen radical-related injury in myocardium and other tissues.
Department of Pharmacology, Kumamoto University Medical School, Honjo, Japan.
T
T
Yamakawa
Y
Y
Kadowaki
M
M
Garcia-Alves
M
M
Yokoyama
Y
Y
Iwashita
K
K
Nishi
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D003327:Coronary Disease / Q000503:physiopathology; D004562:Electrocardiography; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury; D009206:Myocardium / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D011092:Polyethylene Glycols; D008012:Lidocaine; D013482:Superoxide Dismutase