261 Chronic administration of N-acetylcysteine: impact on endothelial dysfunction of epicardial coronary arteries associated with left ventricular hypertrophy in a porcine model

Abstract

The aim of this study was to investigate the potential effect of chronic administration of N-acetylcysteine (NAC), a thiol drug with antioxidant properties, on the coronary endothelial dysfunction associated with LVH. Twenty-two 8-week-old Landrace male swine were randomly divided into 4 experimental groups. The control group (group 1) was submitted to a thoracotomy without aortic banding (AB). The untreated aortic banded group (group 2) was kept for 60 days. The first AB treated group (group 3) received 1000mg/day of NAC per os for 60 days starting on the day of the surgery. The second AB treated group (group 4) received the same oral dose of NAC for 30 days starting on day 30. Hypertrophy was assessed by echocardiography. Coronary vascular reactivity was evaluated in organ chambers. Nitrite/nitrate ratio and glutathione levels were measured to evaluate endothelial dysfunction. Finally, to assess oxidative stress, plasma lipid hydroperoxide levels (LPO) were measured. The LV mass/left ventricular diastolic diameter ratio was significantly higher in group 2 (37.6±10.0 g/cm) compared to group 1 (16.4±1.5 g/cm) confirming the development of LVH. This latest was found to be associated with a significant endothelial dysfunction (maximal relaxation to serotonin 76±2% versus 85±3% for group 1 and 2 respectively; maximal relaxation to bradykinin 100±0% versus 96±1% for group 1 and 2, respectively). NAC did not prevent LVH development in group 3 (30.5±2.3 g/cm; p>0.05 versus group 2) but attenuated its progression in group 4 (25.4±3.0 g/cm). Concentration response curves to NAC showed improvement in endothelium-dependent relaxation to serotonin (55±2% and 57±3% for group 3 and 4, respectively) and to bradykinin (99±1% and 99±1%). LPO levels were significantly lower in both treated group as compared to group 2 (p