Influence of glyceryl trinitrate on venous and arterial effects of chronic, asymmetric isosorbide dinitrate treatment in patients with ischemic heart disease

Abstract

Summary: Asymmetric dosage regimes have been introduced to circumvent development of nitrate tolerance. This study assessed invasively the hemdynamics during supine rest and exercise before and after 4 weeks treatment with 30 mg isosorbide dinitrate (ISDN) or placebo asymmetrically b.i.d. in 14 randomized patients with stable ischemic heart disease in a double-blinded study. An intravenous infusion of glyceryl mnitrate (GTN) was used to assess possible nitrate tolerance. During the initial, medication-free exercise all patients had increased pulmonary arterial wedge pressure ( P A W ) 3 l .4 ? 5.56 mmHg (mean ? SD), showing impaired left ventricular function, while mean arterial pressures (MAP) rose from I 12 ? 16.3 mmHg at rest to 141 2 15.9 mmHgduring exercise. After4 weeks ISDN treatment, mean exercise P A W and MAP, 3 h after morning dose, were reduced to 22.4 f 7.09 mmHg and 127 ? 18.2 mmHg, respectively. Before the ISDN treatment, GTN reduced exercise PAWP to 13.9 ? 5.27 mmHg and MAP to 1 19 f 1 1.2 mniHg, whereas after 4 weeks ISDN treatment, the addition of GTN did not reduce exercise P A W and MAP to the same low levels. Thus, the applied ISDN regimen improved the hemodynamics, but induced a definite, partial nitrate tolerance.