[Nitrate tolerance and its management by N-acetylcysteine (studies of patients with severe chronic heart failure)].

The mechanisms responsible for the development of nitrate tolerance are not completely clear, and their clinical importance remains controversial. This study examined the possible development of nitrate tolerance under the continuous infusion of high doses (10 mg/h) of nitroglycerine (NTG) and the effect of an additional N-acetylcysteine (NAC) injection in respect of hemodynamic changes. Eighteen patients with severe chronic heart failure (NYHA stages III-IV) were investigated. In 16 patients, NTG produced a marked improvement of the hemodynamic parameters; in two patients it caused a moderate amelioration only. In 13 patients there was a complete loss of the initial hemodynamic effect of NTG within 12 to 36 h. NAC reversed the NTG tolerance in 11 out of the 13 patients. In the two patients who showed a milder response to NTG and who did not develop a tolerance, NAC improved the effectiveness of NTG significantly. There was no additional NAC effect in the three patients without NTG tolerance. NAC itself produced no hemodynamic changes. These results confirm the relevance of the depletion of sulfhydryl-groups for the development of nitrate tolerance under the continuous infusion of NTG.