title: Tolerance with low dose intravenous nitroglycerin therapy in acute myocardial infarction.
abstract: The question of vascular tolerance was examined in 154 patients with acute myocardial infarction (64 anterior, 90 inferior) who were treated with prolonged low dose intravenous nitroglycerin in a recent randomized placebo-controlled study. The dose of nitroglycerin was carefully titrated to decrease mean blood pressure by 10% in normotensive patients and 30% in hypertensive (blood pressure greater than 140/90 mm Hg) patients, but not less than 80 mm Hg. Tolerance was defined as the need to increase the dose to maintain this hemodynamic effect. It was labelled "true" if chest pain was absent and "apparent" if chest pain was present. Group analysis of dose, pain scores, hemodynamic, 2-dimensional echocardiographic and clinical parameters monitored serially before and after therapy indicated benefit with nitroglycerin over placebo despite equalizing of blood pressures after 10 hours. Reversal of blood pressures and volumes after discontinuing nitroglycerin suggested lack of significant tolerance. However, detailed individual analysis suggested significant hemodynamic tolerance in 37 patients (24%), both in the true tolerance (12%) and apparent tolerance (12%) subgroups. Tolerance appeared early, requiring the dose to be increased by 30 +/- 39 micrograms/min within 11 +/- 9 hours. The dose was greater (p less than 0.001) in the tolerance than in the no tolerance subgroup, both before (60 vs 27 micrograms/min) and after (90 vs 38 micrograms/min) 10 hours. Tolerance blunted the beneficial effect on infarct size, but positive effects on function, topography and complications persisted.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: B I
authors.initials: BI
authors.lastname: Jugdutt
authors.forename: J W
authors.initials: JW
authors.lastname: Warnica
mesh_terms: D001794:Blood Pressure / Q000187:drug effects; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000627:therapeutic use; D011897:Random Allocation; D013997:Time Factors
chemical_list: D005996:Nitroglycerin