Effects of chronic therapy with nadolol on portal hemodynamics and on splanchnic impedance indices using Doppler sonography: comparison between acute and chronic effects.
OBJECTIVE
Beta-blockers are currently used for chronic therapy of portal hypertension. Duplex Doppler ultrasonography has been proposed for non-invasive evaluation of splanchnic pharmacodynamics, but the chronic effects of beta-blockers on portal hemodynamics and on splanchnic arterial impedance indices have not been analyzed with this method. This was the aim of the study.


METHODS
The effects of acute (80 mg p.o.) and chronic (2 months at a dosage sufficient to reduce heart rate by at least 25% in respect of basal values) nadolol administration on portal blood flow velocity and volume, and on splanchnic and renal arterial impedance indices [pulsatility index = (peak systolic velocity-minimum velocity)/mean velocity] were evaluated in patients with cirrhosis. Twenty-eight patients with cirrhosis and portal hypertension were investigated. Nineteen patients received nadolol, and nine received placebo.


RESULTS
Placebo caused no significant hemodynamic change. Portal blood flow mean velocity decreased after chronic therapy (11.7 +/- 2.9 cm/s to 9.1 +/- 2.3, p < 0.001). In the 16 patients with acute and chronic evaluation, portal blood flow mean velocity decreased after acute therapy (11.8 +/- 3.0 cm/s to 10.4 +/- 3.0, p < 0.01), and even more so after chronic therapy (to 9.2 +/- 2.4, p < 0.01). No parallel was found between acute and chronic effects. Hepatic, mesenteric and splenic pulsatility indices increased after chronic therapy (1.26 +/- 0.33 to 1.39 +/- 0.28, p < 0.02; 2.04 +/- 0.41 to 2.50 +/- 0.61, p < 0.01; 0.92 +/- 0.22 to 1.18 +/- 0.27, p < 0.001 respectively); renal pulsatility index increased (1.12 +/- 0.20 to 1.40 +/- 0.28, p < 0.001).


CONCLUSIONS
Chronic therapy with nadolol decreased portal blood flow velocity and volume, and increased splanchnic and renal impedance indices. Chronic effects of nadolol on portal inflow cannot be predicted from its acute effects. Evaluation of the effect of nadolol on portal blood velocity and volume should be performed after chronic therapy. Duplex Doppler ultrasonography allows venous and arterial splanchnic pharmacodynamics to be studied separately.
Bolognesi
M
M
Servizio di Spleno-Epatologia, Istituto di Medicina Clinica, University of Padua, Italy.
Sacerdoti
D
D
Merkel
C
C
Bombonato
G
G
Enzo
E
E
Gatta
A
A
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D017097:Electric Impedance; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000503:physiopathology; D008875:Middle Aged; D009248:Nadolol / Q000494:pharmacology*; D011168:Portal System / Q000187:drug effects* / Q000503:physiopathology; D018616:Ultrasonography, Doppler, Duplex
D000319:Adrenergic beta-Antagonists; D009248:Nadolol