title: Influence of glyceryl trinitrate on venous and arterial effects of chronic, asymmetric isosorbide dinitrate treatment in patients with ischemic heart disease.
abstract: Asymmetric dosage regimes have been introduced to circumvent development of nitrate tolerance. This study assessed invasively the hemodynamics 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 trinitrate (GTN) 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 impaired left ventricular function, while mean arterial pressures (MAP) rose 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 morning 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 weeks ISDN treatment, the addition of GTN did not reduce exercise PAWP and MAP to the same low levels. Thus, the applied ISDN regimen improved the hemodynamics, but induced a definite, partial nitrate tolerance.
authors.affiliation: Department of Clinical Physiology, Ullevål Hospital, Oslo, Norway.
authors.forename: L H
authors.initials: LH
authors.lastname: Jørgensen
authors.forename: H E
authors.initials: HE
authors.lastname: Refsum
authors.forename: E
authors.initials: E
authors.lastname: Thaulow
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004361:Drug Tolerance; D005080:Exercise Test; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D005996:Nitroglycerin / Q000494:pharmacology*; D012146:Rest
chemical_list: D005996:Nitroglycerin; D007548:Isosorbide Dinitrate