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PREVENTIVE ADMINISTRATION OF INTRAVENOUS N-ACETYLCYSTEINE AND DEVELOPMENT OF TOLERANCE TO ISOSORBIDE DINITRATE IN PATIENTS WITH ANGINA-PECTORIS

BOESGAARD, S ; ALDERSHVILE, J ; POULSEN, HE

Circulation (New York, N.Y.), 1992-01, Vol.85 (1), p.143-149 [Revista revisada por pares]

DALLAS: Amer Heart Assoc

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Título:
PREVENTIVE ADMINISTRATION OF INTRAVENOUS N-ACETYLCYSTEINE AND DEVELOPMENT OF TOLERANCE TO ISOSORBIDE DINITRATE IN PATIENTS WITH ANGINA-PECTORIS
Autor: BOESGAARD, S ; ALDERSHVILE, J ; POULSEN, HE
Materias: Acetylcysteine - therapeutic use ; Adult ; Aged ; Angina Pectoris - drug therapy ; Angina Pectoris - physiopathology ; Antianginal agents. Coronary vasodilator agents ; Biological and medical sciences ; Cardiac & Cardiovascular Systems ; Cardiovascular system ; Cardiovascular System & Cardiology ; Double-Blind Method ; Drug Combinations ; Drug Tolerance ; Exercise Test ; Hemodynamics ; Humans ; Injections, Intravenous ; Isosorbide Dinitrate - therapeutic use ; Life Sciences & Biomedicine ; Medical sciences ; Middle Aged ; Peripheral Vascular Disease ; Pharmacology. Drug treatments ; Rest ; Science & Technology
Es parte de: Circulation (New York, N.Y.), 1992-01, Vol.85 (1), p.143-149
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
ObjectType-News-3
content type line 23
Descripción: Background. Development of tolerance to organic nitrates may be related to depletion of sulfhydryl groups in vascular smooth muscle. N-Acetylcysteine (NAC), a sulfhydryl donor, has been reported to potentiate the effect of nitroglycerin and reverse tolerance in humans. However, its ability to prevent or delay the development of nitrate tolerance in patients with angina pectoris has not been established. Methods and Results. Ten patients with stable angina pectoris were treated with intravenous isosorbide dinitrate (ISDN; 5 mg/hr) combined with NAC (2 g i.v. over 15 minutes followed by 5 mg/kg/hr) or matching placebo for 30 hours in a double-blind, randomized, crossover study with a washout interval of 8 days. Bicycle exercise tests were performed before and at 1 1/2, 8, 20, 24, and 30 hours after start of treatment. After 24 hours of infusion, exercise parameters were not significantly different from pretreatment values (p > 0.05) during ISDN plus placebo, indicating development of tolerance to ISDN. In contrast, time to onset of angina, time to 1-mm ST segment depression, and total amount of ST segment depression were still significantly improved after 24-hour infusion of ISDN plus NAC (p < 0.05). In addition, compared with placebo, a significant difference (p < 0.05) in favor of NAC was observed regarding time to angina (507 +/- 63 versus 445 +/- 69 seconds, mean +/- SEM), time to 1-mm ST segment depression (435 +/- 43 versus 407 +/- 45 seconds), and total ST segment depression (1.8 +/- 0.9 versus 3.1 +/- 0.4 mm). Conclusions. These results suggest that infusion of high doses of NAC in combination with ISDN for 30 hours affects and partially prevents the development of tolerance to antianginal effects normally observed during infusion with ISDN.
Editor: DALLAS: Amer Heart Assoc
Idioma: Inglés

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PREVENTIVE ADMINISTRATION OF INTRAVENOUS N-ACETYLCYSTEINE AND DEVELOPMENT OF TOLERANCE TO ISOSORBIDE DINITRATE IN PATIENTS WITH ANGINA-PECTORIS

BOESGAARD, S ; ALDERSHVILE, J ; POULSEN, HE

DALLAS: Amer Heart Assoc

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