Evaluation of Cross-Tolerance Between Long-Term Oral Isosorbide Dinitrate and Sublingual Nitroglycerin: Assessment by Exercise Testing

Abstract

Recent studies have documented the ability of orally administered isosorbide dinitrate (ISDN), when administered in sufficiently large doses, to induce beneficial antianginal effects in patients with coronary artery disease (1–4). Accordingly, enhanced exercise tolerance, alleviation of symptoms, reduced electrocardiographic manifestations of myocardial ischemia, and favorable alterations in cardiocirculatory hemodynamics have all been demonstrated after the oral administration of ISDN (1–13). However, the question of whether or not chronic oral consumption of isosorbide induces tolerance to the nitrate effect remains unresolved. In particular, the ability of chronic oral isosorbide administration to abolish the acute response to sublingual nitroglycerin would have major implications regarding the application of this agent in patients with coronary disease. The issue of induction of tolerance to sublingually administered nitroglycerin by orally administered ISDN has assumed greater importance in view of the increased application of this agent in patients with ischemic heart disease in recent years. Therefere, we conducted a study to assess the effects of long-term oral administration of ISDN on the antianginal response to nitroglycerin by means of exercise stress testing.