title: Different mechanisms of isoproterenol-induced and nitroglycerin-induced syncope during head-up tilt in patients with unexplained syncope: important role of epinephrine in nitroglycerin-induced syncope.
abstract: BACKGROUND
  A reduction in left ventricular volume and an increase in epinephrine levels have been reported in tilt-induced neurally mediated syncope. To compare the mechanisms of isoproterenol-induced and nitroglycerin-induced syncope during head-up tilt and to investigate the role of catecholamines, the temporal changes in plasma levels of norepinephrine and epinephrine and in left ventricular volume were measured.
  
  
  RESULTS
  The first study population consisted of 90 patients with syncope of unknown etiology and 12 control subjects. The second study population consisted of 43 patients with unexplained syncope. In the first study, head-up tilt (80 degree angle) was conducted for 40 minutes, and norepinephrine and epinephrine levels were measured. In the second study, all patients were randomly allocated to either isoproterenol test (20 patients) or nitroglycerin test (23 patients) for 20-minute head-up tilt. Isoproterenol infusion was given at a rate of 1 to 3 microg/min. Intravenous infusion of nitroglycerin was started at 250 microg/hour with increasing dosages up to 1,500 microg/hour. Norepinephrine and epinephrine were measured in peripheral venous blood. Left ventricular volumes were measured by echocardiography with patients in the supine position and during head-up tilt every 1 minute. End-diastolic volume and end-systolic volume were calculated. In the first study, 61 patients demonstrated a positive response and 29 patients demonstrated a negative response. Plasma norepinephrine changes during head-up tilt were not significantly different, whereas epinephrine levels were significantly higher in the positive patients than in the negative and control subjects (148 +/- 118 pg/mL vs 66 +/- 31 pg/mL and 55 +/- 27 pg/mL). Thirteen of the 20 patients given isoproterenol and 15 of the 23 patients given nitroglycerin showed a positive head-up tilt (65.0% vs 65.2%; P = NS). During isoproterenol and nitroglycerin infusion head-up tilt, epinephrine in the positive group determined by the nitroglycerin test was significantly higher than that in the other three groups (103 +/- 38 pg/mL vs 60 +/- 33 pg/mL, 31 +/- 21 pg/mL, and 50 +/- 52 pg/mL). In contrast, end-systolic volume was significantly smaller in the positive group than in the other three groups based on findings of the isoproterenol test.
  
  
  CONCLUSIONS
  The findings suggest that nitroglycerin triggers head-up tilt-induced syncope by increasing epinephrine levels, whereas isoproterenol induces syncope by decreasing left ventricular volume.
authors.affiliation: Department of Internal Medicine-1, National Defense Medical College, Tokorozawa, Saitama, Japan. dui1577@db3.so-net.ne.jp
authors.forename: B
authors.initials: B
authors.lastname: Takase
authors.forename: A
authors.initials: A
authors.lastname: Uehata
authors.forename: T
authors.initials: T
authors.lastname: Nishioka
authors.forename: K
authors.initials: K
authors.lastname: Isojima
authors.forename: K
authors.initials: K
authors.lastname: Satomura
authors.forename: F
authors.initials: F
authors.lastname: Ohsuzu
authors.forename: A
authors.initials: A
authors.lastname: Kurita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001810:Blood Volume; D004837:Epinephrine / Q000097:blood / Q000502:physiology*; D005260:Female; D018475:Head-Down Tilt; D006801:Humans; D007545:Isoproterenol; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin; D009638:Norepinephrine / Q000097:blood; D013575:Syncope / Q000139:chemically induced* / Q000503:physiopathology*; D016277:Ventricular Function, Left
chemical_list: D005996:Nitroglycerin; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine