Am. J. Respir. Crit. Care Med., Vol 154, No. 5, Nov 1996, 1347-1350.
Effects of chronic dexfenfluramine treatment on pulmonary hemodynamics in dogs
R Naeije, M Maggiorini, M Delcroix, M Leeman and C Melot
Laboratory of Cardiovascular and Respiratory Physiology, Erasme University Hospital, Brussels, Belgium.
An epidemic of primary pulmonary hypertension occurred in Europe in the
1960s, after the introduction of the appetite suppressant aminorex.
Recently, a cluster of cases of pulmonary hypertension was observed in
France in relation to the intake of the appetite suppressant
dexfenfluramine. We previously reported that intravenous dexfenfluramine
enhances hypoxic pulmonary vasoconstriction in dogs. We therefore
investigated the pulmonary hemodynamic effects of chronic oral intake of
this drug. Twenty-four dogs with a strong (n = 12) and a weak hypoxic
pulmonary vasoconstriction (n = 12) respectively were randomly allocated in
a double blind manner to a twice daily oral intake of either a placebo or
dexfenfluramine 1.5 mg/kg for 20 d. A strong hypoxic vasoconstriction was
defined as a hypoxia-induced increase in pulmonary artery pressure by more
than 3 mm Hg at a standardized cardiac output of 3 L/min/m2. Pulmonary
hemodynamics were studied in hyperoxia (fraction of inspired O2 [F(I)O2]
0.4) and in hypoxia (F(I)O2 0.1) before and after treatment. Venous return
was manipulated at post-treatment evaluation for isoflow comparisons of
pulmonary vascular pressures. Dexfenfluramine had no effect on systemic
hemodynamics or blood gases, but increased pulmonary vascular resistance
from 155 +/- 17 to 192 +/- 14 dyne x s x cm(-5) in hyperoxia (mean +/- SE,
p < 0.05) and from 237 +/- 27 to 293 +/- 47 dyne x s x cm(-5) in hypoxia
(p < 0.01). Dexfenfluramine, and not placebo, increased the isoflow
pulmonary vascular pressure gradient in hyperoxia and in hypoxia. This
effect was unrelated to the magnitude of pretreatment hypoxic
vasoconstriction. We conclude that the chronic intake of dexfenfluramine in
dogs is associated with a moderate increase in pulmonary vascular
resistance which is unrelated to pulmonary vasoreactivity to hypoxia.
