Lipid peroxidation and antioxidant status following thrombolytic therapy for acute myocardial infarction

We have investigated the timescale of increased lipid peroxidationfollowing successful early thrombolytic therapy for acute myocardialinfarction and report for the first time reciprocal changesin plasma chain-breaking antioxidants. Sixty-seven patientswere recruited following a first acute myocardial infarctionwithin 6 h of the onset of symptoms and received 70 or 100 mgof recombinant tissue plasminogen activator (Actilyse) as twointravenous bolus injections 30 min apart. Serial blood sampleswere taken before administration of thrombolytic therapy andafter 30 min, 60 min, 90 min, 6 h and 24 h. Coronary arterypatency was assessed at 90 min by coronary angiography. Malondialdehyde(MDA), a marker of lipid peroxidation, and the chain-breakingantioxidants alpha-tocopherol, retinol and ascorbate were measuredby high performance liquid chromatography. When the coronaryartery was patent there was an early rise in plasma MDA (time0.091 ± 0.05 µmol.l^–1) with levels peakingat 90 min (1.02 ± 0.06, P<0.05) and returning to baselineby 6 h (0.85 ± 0.06), accompanied by reciprocal decreasesin alpha-tocopherol (time 0 7.13 ± 0.34 µmol.mmol^–1cholesterol, 90 min 6.64±0.33, P<0.05) and retinol(time 0 1.99±0.10 µmol.l^–1, 90 min 1.81 ±0.08, P<0.05). Ascorbate levels did not change significantlyuntil 24 h (time 0 29.5 ± 4.9 µmol.l^–1, 24h 22.6 ± 4.4, P<0.05). Where the coronary artery wasoccluded no changes in these parameters were found except fora late (24 h) fall in ascorbate (time 0 18.5 ± 2.0 mol.l^–1,24 h 12.2 ± 2.2, P<0.05). The timescale of changesin MDA and antioxidants supports a role for increased free radicalproduction following successful early thrombolytic therapy foracute myocardial infarction.