Hemodynamic effects of the somatostatin analog lanreotide in humans: placebo-controlled, cross-over dose-ranging Echo-Doppler study.
Because of their vasoactive effects, somatostatin and its analogs are increasingly used in the management of complications of chronic liver diseases such as variceal bleeding. Postprandial hyperemia augments splanchnic blood flow, subsequently increasing portal pressure. The aim of this study was to explore effects of the somatostatin analog, lanreotide, on food-stimulated hemodynamic parameters in healthy human subjects. A dose-response curve was constructed in eight healthy male subjects in a placebo-controlled cross-over study. On 4 different days, either 0 (placebo), 50, 100, or 200 microg/h of lanreotide was infused intravenously in random order, starting at 45 minutes for 7 hours. On each day, a liquid test meal (Ensure plus, 1.5 kcal/mL) was perfused intraduodenally at a rate of 3 mL/min over 7 hours after a 45-minute basal period. Diastolic arterial pressure (dBP), heart rate (HR), superior mesenteric arterial (SMA) average flow velocity (SMA-V), SMA pulsatility index (SMA-PI), portal venous volume flow (PV-F), and renal artery (RA) resistance index (RA-RI) were measured on regular intervals (flows using Echo-Doppler technology). Lanreotide at all doses abolished food-stimulated splanchnic hyperemia both in the SMA and PV over 7 hours. The fall in dBP and increase in HR after food perfusion were blunted under lanreotide. Food as well as lanreotide did not modify RA-RI. In summary: 1) lanreotide inhibits food-induced splanchnic hyperemia in normal subjects; 2) in parallel, systemic hemodynamic alterations to food stimulation are abolished with lanreotide; and 3) renal vascular resistance is unchanged. Because of its persistent splanchnic vasoconstrictive effect, lanreotide should be tested in patients with portal hypertension.
Mottet
C
C
Division of Gastroenterology, University Hospital, Basel, Switzerland.
Sieber
C C
CC
Nauer
A
A
Drewe
J
J
Fried
R
R
Larsen
F
F
Beglinger
C
C
D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005502:Food; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D010456:Peptides, Cyclic / Q000493:pharmacokinetics / Q000494:pharmacology*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects
D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin