Reperfusion arrhythmias: dose-related protection by anti-free radical interventions.
Isolated rat hearts (n = 15 per group) were subjected to regional ischemia (10 min) and reperfusion. Superoxide dismutase (SOD; 8 X 10(3), 2 X 10(4), 4 X 10(4), 6 X 10(4), 8 X 10(4), 1.2 X 10(5), or 1.6 X 10(5) IU/l) given early (i.e., throughout the experiment) reduced the incidence of reperfusion-induced ventricular fibrillation (VF), the dose-response characteristics describing an asymmetric U-shaped curve. The optimal dose of SOD (8 X 10(4) IU/l) reduced VF incidence from its control value of 87 to 27% (P less than 0.05). Given late (i.e., 2 min before reperfusion), this dose of SOD exerted a reduced but nonetheless significant antifibrillatory effect. Early administration of catalase (1 X 10(3), 1 X 10(4), 2.5 X 10(4), 5 X 10(4), 1 X 10(5), 1.5 X 10(5), or 1 X 10(6) IU/l) reduced VF incidence in a linear dose-dependent manner, from its control value of 87 to 7% with 1 X 10(6) IU/l (P less than 0.05). Late administration of this dose reduced VF incidence from its control value of 87 to 27% (P less than 0.05). Allopurinol (0.07, 0.15, 0.37, 0.73, 1.10, or 1.47 mM added to the perfusate throughout the experiment) significantly reduced VF incidence over a wide range of doses, but low and high doses were ineffective. Pretreatment with allopurinol (0, 0.01, 0.02, 0.05, 0.10, 0.20, or 0.50 g.kg-1.day-1 per os 48, 24, and 1 h before study) reduced VF incidence from its control value of 93 to less than 50% at several doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Bernier
M
M
Rayne Institute, St. Thomas' Hospital, London, United Kingdom.
Manning
A S
AS
Hearse
D J
DJ
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000517:prevention & control; D002374:Catalase / Q000494:pharmacology*; D003327:Coronary Disease / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D005609:Free Radicals; D000493:Allopurinol; D002374:Catalase; D013482:Superoxide Dismutase