title: Dose-dependent benefit of nitroglycerin on microcirculation of patients with severe heart failure.
abstract: BACKGROUND
  Microcirculatory abnormalities are frequently observed in patients with severe heart failure and correlate to worse outcomes. We tested the hypothesis that nitroglycerin dose-dependently improves perfusion in severe heart failure and that this could be monitored by measuring central-peripheral temperature gradient and with Sidestream Dark Field imaging of the sublingual mucosa.
  
  
  METHODS
  A dose-response study was performed in 17 patients with cardiogenic shock (n = 9) or end-stage chronic heart failure (n = 8) admitted to Erasmus University Medical Center. We did hemodynamic measurements at baseline and during increasing infusion rates of nitroglycerin (up to a maximum dose of 133 microg min(-1)). As parameters of tissue perfusion, we measured central-peripheral temperature gradient (delta-T) and sublingual perfused capillary density (PCD).
  
  
  RESULTS
  Nitroglycerin dose-dependently decreased mean arterial pressure (p < 0.001) and cardiac filling pressures (both central venous pressure (CVP) and pulmonary capillary wedge pressure: p < 0.001). It increased cardiac index (p = 0.01). Nitroglycerin decreased delta-T (p < 0.001) and increased sublingual PCD (p < 0.001). Significant changes in delta-T and PCD occurred earlier, i.e., at a lower doses of NTG, than changes in global hemodynamics. Macrohemodynamic and microcirculatory responses to nitroglycerin infusion were consistent in patients with either cardiogenic shock or end-stage chronic heart failure. Changes in microcirculatory parameters occurred independently of changes in cardiac index.
  
  
  CONCLUSIONS
  Nitroglycerin dose-dependently increases tissue perfusion in patients with severe heart failure, as observed by a decrease in central-peripheral temperature gradient and an increase in sublingual perfused capillary density.
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus Medical Center, s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. c.denuil@erasmusmc.nl
authors.forename: Corstiaan A
authors.initials: CA
authors.lastname: den Uil
authors.forename: Kadir
authors.initials: K
authors.lastname: Caliskan
authors.forename: Wim K
authors.initials: WK
authors.lastname: Lagrand
authors.forename: Martin
authors.initials: M
authors.lastname: van der Ent
authors.forename: Lucia S D
authors.initials: LS
authors.lastname: Jewbali
authors.forename: Jan P
authors.initials: JP
authors.lastname: van Kuijk
authors.forename: Peter E
authors.initials: PE
authors.lastname: Spronk
authors.forename: Maarten L
authors.initials: ML
authors.lastname: Simoons
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D009060:Mouth Floor / Q000098:blood supply / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000494:pharmacology; D012770:Shock, Cardiogenic / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D049489:Stroboscopy; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin