title: Predictors of inotropic and chronotropic effects of NG-monomethyl-L-arginine.
abstract: BACKGROUND
  The haemodynamic effects of intravenous infusion of the non-selective nitric oxide synthase (NOS) L-omega monomethyl arginine (L-NMMA) have previously been characterized in humans. Its effect of reducing cardiac index (CI) is an important reason for the increase in mortality in patients with septic shock receiving L-NMMA in a pivotal outcome trial for this indication. The mechanism for the reduction in CI however, is uncertain.
  
  
  METHODS
  In this study, we investigated the haemodynamic and arterial stiffness response to a bolus intravenous infusion of L-NMMA (3 mg kg(-1) over 5 min) in 26 healthy human volunteers to clarify the likely cause of L-NMMA induced negative inotropic and chronotropic effects. Digital photoplethysmography (MicroMedical Pulse Trace) was used to derive two measures of arterial stiffness: stiffness index, a measure of large arterial stiffness, and reflection index (RI), a measure of small- to medium-sized arterial stiffness. Haemodynamic measurements of systolic blood pressure, diastolic blood pressure, heart rate, systemic vascular resistance index (SVRI), stroke index and CI were made using a bioimpedance monitor (BioZ Cardiodynamics).
  
  
  RESULTS
  We found that changes in CI during L-NMMA are closely related to changes in RI and SVRI.
  
  
  CONCLUSIONS
  The negative inotropic effect of L-NMMA may be a result of an increase in coronary vascular resistance and a resultant decrease in myocardial perfusion. The reduction in CI may also result from a direct reduction of the normal positive inotropic effect of NO by L-NMMA which is closely correlated with its effects on SVRI.
authors.affiliation: Department of Medicine, University of New South Wales, Chapel St Kogarah, NSW, Australia.
authors.forename: D G
authors.initials: DG
authors.lastname: Brillante
authors.forename: A J
authors.initials: AJ
authors.lastname: O'Sullivan
authors.forename: M T
authors.initials: MT
authors.lastname: Johnstone
authors.forename: L G
authors.initials: LG
authors.lastname: Howes
mesh_terms: D000328:Adult; D001158:Arteries / Q000187:drug effects*; D001783:Blood Flow Velocity / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000494:pharmacology; D012044:Regression Analysis; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase