title: Effect of nitric oxide synthase inhibition on haemodynamics and outcome of patients with persistent cardiogenic shock complicating acute myocardial infarction: a phase II dose-ranging study.
abstract: OBJECTIVE
  Previous studies suggested haemodynamic benefits and, possibly, mortality reduction with the use of nitric oxide synthase (NOS) inhibition in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). We assessed preliminary efficacy and safety of four doses of l-n-monomethyl-arginine (l-NMMA), a non-selective NOS inhibitor, in patients with AMI complicated by CS despite an open infarct-related artery.
  
  
  RESULTS
  Patients (n = 79) were randomly assigned to a bolus and 5 h infusion of placebo or 0.15, 0.5, 1.0, or 1.5 mg/kg of l-NMMA. The primary outcome measure was absolute change in mean arterial pressure (MAP) at 2 h. Fifteen minutes after study drug initiation, mean change in MAP was -4.0 mmHg in the placebo group and 5.8 (P = 0.02), 4.8 (P = 0.02), 5.1 (P = 0.07), and 11.6 (P < 0.001) mmHg in the four l-NMMA groups, respectively (all vs. placebo). Mean change in MAP at 2 h was -0.4, 4.4, 1.8, -4.1, and 6.8 mmHg in the placebo and four l-NMMA groups, respectively (all P = NS).
  
  
  CONCLUSIONS
  l-NMMA resulted in modest increases in MAP at 15 min compared with placebo but there were no differences at 2 h.
authors: University Health Network, Toronto General Hospital, 6-246, 200 Elizabeth Street, Toronto M5G 2C4, Ontario, Canada. vlad.dzavik@uhn.on.ca
authors: Vladimir
authors: V
authors: Dzavík
authors: Gad
authors: G
authors: Cotter
authors: Harmony R
authors: HR
authors: Reynolds
authors: John H
authors: JH
authors: Alexander
authors: Krishnan
authors: K
authors: Ramanathan
authors: Amanda L
authors: AL
authors: Stebbins
authors: David
authors: D
authors: Hathaway
authors: Michael E
authors: ME
authors: Farkouh
authors: E Magnus
authors: EM
authors: Ohman
authors: David A
authors: DA
authors: Baran
authors: Roland
authors: R
authors: Prondzinsky
authors: Julio A
authors: JA
authors: Panza
authors: Warren J
authors: WJ
authors: Cantor
authors: Zvi
authors: Z
authors: Vered
authors: Christopher E
authors: CE
authors: Buller
authors: Neal S
authors: NS
authors: Kleiman
authors: John G
authors: JG
authors: Webb
authors: David R
authors: DR
authors: Holmes
authors: Joseph E
authors: JE
authors: Parrillo
authors: Stanley L
authors: SL
authors: Hazen
authors: Steven S
authors: SS
authors: Gross
authors: Robert A
authors: RA
authors: Harrington
authors: Judith S
authors: JS
authors: Hochman
mesh_terms: D000368:Aged; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000201:enzymology / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012770:Shock, Cardiogenic / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase