Different haemodynamic effects of a single dose of long-acting isosorbide-5-mononitrate in healthy subjects and patients with cirrhotic portal hypertension.
BACKGROUND
The action pathways of nitrates are hypothesised to be deranged in cirrhosis.


OBJECTIVE
In order to confirm it, the acute haemodynamic effects of isosorbide-5-mononitrate in cirrhotic patients and controls was investigated.


METHODS
Nine cirrhotics and nine healthy controls.


METHODS
Evaluation in the fasting state, 90 min after isosorbide-5-mononitrate or placebo (double-blind on two different days) and then 30 and 120 min after eating a standard meal. Various systemic and splanchnic haemodynamic parameters, including arterial impedance, assessed as Doppler pulsatility index, were measured.


RESULTS
isosorbide-5-mononitrate reduced arterial pressure and increased heart rate and mesenteric pulsatility index both in controls and in cirrhotics, whereas the following parameters behaved differently in the two groups (P < 0.05): hepatic pulsatility index decreased (-9%) and the portal velocity increased (+13%) in controls, whereas hepatic pulsatility increased (+18%) and portal velocity decreased (-18%) in cirrhotics. The two groups presented a similar pattern of changes in most variables under placebo after a meal. In controls, the administration of isosorbide-5-mononitrate blunted the postprandial mesenteric vasodilation and related changes in splanchnic and systemic circulation, expected at 30 min, in comparison to those observed under placebo. In cirrhotics, instead, the postprandial pattern was similar under placebo and isosorbide-5-mononitrate.


CONCLUSIONS
The acute administration of isosorbide-5-mononitrate produces different haemodynamic effects in healthy and diseased livers, both in the fasting state and after a meal, consistent with the hypothesis of a deranged response of the intrahepatic microcirculation to nitrates in cirrhosis.
Division of Internal Medicine, Department of Internal Medicine and Gastroenterology, University of Bologna, Azienda S Orsola-Malpighi, via Albertoni 15, 40138 Bologna, Italy. Piscagl@med.unibo.it
F
F
Piscaglia
G
G
Donati
S
S
Gaiani
L
L
Gramantieri
S
S
Leoni
M
M
Mancini
L
L
Bolondi
D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D017082:Portal Pressure / Q000187:drug effects*; D011169:Portal Vein / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate