Allopurinol and reperfusion-induced arrhythmias: increased protection by simultaneous administration of anti-oxidant enzymes.
We have assessed whether the xanthine oxidase inhibitor, allopurinol, can afford maximal protection against the formation of reperfusion-induced arrhythmias or whether the addition of free radical scavengers and anti-oxidants can increase this protection. Using an anesthetized rat preparation with transient coronary artery occlusion, we have compared the ability of allopurinol pretreatment alone to that of a combination therapy of allopurinol, superoxide dismutase, and catalase to reduce the incidence of reperfusion-induced arrhythmias. While both regimes reduced the incidence of reperfusion-induced ventricular fibrillation (from 87% to 40%, p less than 0.05 by allopurinol alone; and to 13%, p less than 0.01 by combination therapy), and both treatments eliminated mortality, only combination therapy reduced the incidence of reperfusion-induced ventricular tachycardia (from 87% to 40%, p less than 0.05). Furthermore, using an arrhythmia score analysis, combination therapy was shown to offer significantly greater protection than allopurinol alone. This additional protection afforded by combination therapy was also demonstrated by significant decreases in log10 duration of fibrillation and log10 number of premature ventricular complexes compared with allopurinol alone. Both allopurinol and combination therapy also significantly delayed the ischemia-induced increases in ST segment elevation, although there was no difference between the two drug-treated groups. We conclude from these results that allopurinol does not offer maximal protection against reperfusion-induced arrhythmias and that the addition of more general anti-oxidant therapy can increase this protection.
Crome
R
R
Department of Biology, Roche Products Limited, Welwyn Garden City, Hertfordshire, England.
Manning
A S
AS
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D057487:Enzyme Therapy; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000627:therapeutic use
D000975:Antioxidants; D000493:Allopurinol; D013482:Superoxide Dismutase