N-ACETYLCYSTEINE ATTENUATES NITROGLYCERIN TOLERANCE IN PATIENTS WITH ANGINA-PECTORIS AND NORMAL LEFT-VENTRICULAR FUNCTION

The aim of this study was to assess whether N-acetylcysteine (NAG) is able to prevent tolerance to a 48-hour infusion of nitroglycerin (NTG) in the setting of normal left ventricular function. In 16 patients, t he hemodynamic response to 0.8 mg sublingual (s.l.) NTG was assessed b y measuring mean arterial, pulmonary artery, pulmonary capillary wedge and right atrial pressures, cardiac output, and calculation of the sy stemic and pulmonary vascular resistances. The parameters were obtaine d at baseline and 1 to 10 minutes after the s.l. NTG application (day 1). NTG was started at 1.5 mu g/kg/min; concomitantly, a bolus of 2,00 0 mg of NAC was administered, followed by an infusion of 5 mg/kg/hour. Both infusions were continued for 48 hours, and the hemodynamic study was repeated (day 3). The same measurements were obtained in a matche d control group of 15 patients with NTG infusion alone. plasma renin a ctivity, aldosterone, and norepinephrine were measured before and afte r the infusion period. The first s.l. NTG infusion (day 1) caused a si gnificant decrease in mean arterial (p < 0.01), pulmonary artery (p < 0.001), and right atrial pressures (p < 0.001), and in systemic (p < 0 .01) and pulmonary vascular resistances (p < 0.001) in both groups. Af ter the 48-hour infusion (day 3), there was a total loss of nitrate-me diated vasodilation (pressure values and vascular resistances day 3 > day 1) in 5 of 16 patients (NAG nonresponders), whereas in the other 1 1 of 16 patients (NAG responders), there was significant vasodilation throughout the infusion period. Tolerance had developed in 14 of 15 pa tients with NTG infusion alone. The same difference (responder vs nonr esponder vs NTG alone) held true regarding the response to the second s.l. NTG infusion after 48 hours. The neurohormonal counter-regulation and intravascular volume expansion (increase in plasma renin activity , p < 0.001, and norepinephrine, p < 0.05; decrease in aldosterone, p < 0.01) did not differ between responders and nonresponders. We conclu de that NAC attenuates tolerance development to a continuous NTG infus ion in a specific patient subgroup and that this occurs despite the sa me amount of neurohormonal counter-regulation and intravascular volume expansion compared with patients with tolerance development. (C) 1997 by Excerpta Medica, Inc.