Dose-dependent benefit of nitroglycerin on microcirculation of patients with severe heart failure.
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.
den Uil
Corstiaan A
CA
Department of Cardiology, Thoraxcenter, Erasmus Medical Center, s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. c.denuil@erasmusmc.nl
Caliskan
Kadir
K
Lagrand
Wim K
WK
van der Ent
Martin
M
Jewbali
Lucia S D
LS
van Kuijk
Jan P
JP
Spronk
Peter E
PE
Simoons
Maarten L
ML
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
D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin