title: Escalating nitrate dose overcomes early attenuation of hemodynamic effect caused by nitrate tolerance in patients with heart failure.
abstract: This study was performed to examine the hypothesis that an early attenuation of nitrate effect caused by nitrate tolerance can be overcome by dose increase. We compared hemodynamic effects of constant dose (40 to 120 mg) of oral isosorbide dinitrate (ISDN) given every 6 hours for three doses followed by 12 hours of nitrate washout interval with those of escalating dose (40 mg, 80 mg, and 120 mg) in two similar groups of patients with chronic congestive heart failure. Escalating ISDN dose resulted in a progressive increase in ISDN blood level and overcame early attenuation of effect occurring with a constant dose. At peak effect of the third ISDN dose, a significantly greater reduction was seen in mean right atrial pressure (-59% +/- 27% vs -20% +/- 22%, p < 0.01), mean pulmonary artery pressure (-29% +/- 11% vs -11% +/- 15%, p < 0.01) and mean pulmonary artery wedge pressure (-39% +/- 19% vs -19% +/- 23%, p < 0.05) with the escalating dose. These findings demonstrate that early attenuation of hemodynamic effect caused by nitrate tolerance can be overcome by dose escalation.
authors.affiliation: Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mehra
authors.forename: A
authors.initials: A
authors.lastname: Shotan
authors.forename: E
authors.initials: E
authors.lastname: Ostrzega
authors.forename: J
authors.initials: J
authors.lastname: Vasquez-Johnson
authors.forename: U
authors.initials: U
authors.lastname: Elkayam
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure; D004361:Drug Tolerance; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery / Q000502:physiology; D011669:Pulmonary Wedge Pressure; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D007548:Isosorbide Dinitrate