N-ACETYLCYSTEINE IN COMBINATION WITH NITROGLYCERIN AND STREPTOKINASE FOR THE TREATMENT OF EVOLVING ACUTE MYOCARDIAL-INFARCTION - SAFETY ANDBIOCHEMICAL EFFECTS

Background N-acetylcysteine (NAC) has been shown to potentiate the eff ects of nitroglycerin (NTG) and to have antioxidant activity. This is the first study to assess the safety and effect of NAC in the treatmen t of evolving acute myocardial infarction (AMI). Methods and Results P atients with AMI received either 15 g NAC infused over 24 hours (n=20) or no NAC (n=7), combined with intravenous NTG and streptokinase. Per ipheral venous plasma malondialdehyde (MDA), reduced (GSH) and oxidize d (GSSG) glutathione concentrations, and rate of reperfusion (using co ntinuous ST-segment analysis) were measured. Cardiac catheterization w as performed between days 2 and 5. No significant adverse events occur red. Less oxidative stress occurred in patients treated with NAC than in patients not receiving NAC (GSH to GSSG ratio 44+/-25 versus 19+/-1 3 at 4 hours, P<.05). NAC concentration (mean 172+/-79 mu mol/L at 4 h ours) was correlated to GSH concentration (P=.006). MDA concentrations were lower (P=.001) over the first 8 hours of treatment with NAC. The re was a trend toward more rapid reperfusion (median 58 minutes, 95% c onfidence interval [CI] 48 to 98 minutes versus median 95 minutes, 95% CI 59 to 106 minutes; P=.17) and better preservation of left ventricu lar function (cardiac index 3.4+/-0.8 versus 2.6+/-0.27 L . min . m(2) , P=.009) with NAC treatment. Conclusions NAC in combination with NTG and streptokinase appeared to be safe for the treatment of evolving AM I and was associated with significantly less oxidative stress, a trend toward more rapid reperfusion, and better preservation of left ventri cular function.