INFLUENCE OF GLYCERYL TRINITRATE ON VENOUS AND ARTERIAL EFFECTS OF CHRONIC, ASYMMETRIC ISOSORBIDE DINITRATE TREATMENT IN PATIENTS WITH ISCHEMIC-HEART-DISEASE

Asymmetric dosage regimes have been introduced to circumvent developme nt of nitrate tolerance. This study assessed invasively the hemodynami cs 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 do uble-blinded study. An intravenous infusion of glyceryl trinitrate (GT N) was used to assess possible nitrate tolerance. During the initial, medication-free exercise all patients had increased pulmonary arterial wedge pressure (PAWP) 31.4 +/- 5.56 mmHg (mean +/- SD), showing impai red left ventricular function, while mean arterial pressures (MAP) ros e from 112 +/- 16.3 mmHg at rest to 141 +/- 15.9 mmHg during exercise. After 4 weeks ISDN treatment, mean exercise PAWP and MAP, 3 h after m orning dose, were reduced to 22.4 +/- 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 119 +/- 11.2 mmHg, whereas after 4 week s ISDN treatment, the addition of GTN did not reduce exercise PAWP and MAP to the same low levels. Thus, the applied ISDN regimen improved t he hemodynamics, but induced a definite, partial nitrate tolerance.