6 research outputs found
Pulmonary haemodynamics are correlated with intimal lesions in a rat model of severe PAH: attenuation of pulmonary vascular remodelling with ambrisentan
Rationale: Pulmonary arterial hypertension
(PAH) is characterized by obstructive lesions and
vasoconstriction of the pulmonary arteries. Early
therapeutic interventions with vasodilator drugs are
thought to be beneficial in PAH. However, it remains
unknown whether the severity of intimal obstruction is
associated with increased pulmonary arterial pressure
and whether reduction of vasoconstriction in the earlier
stage by these drugs has a beneficial effect. Therefore,
the aims of this study were to investigate these issues in
a rat model of severe PAH. Methods: A rat model of
severe PAH was created by injection of a vascular
endothelial growth factor receptor blocker in
combination with hypoxia for the first 3 weeks followed
by normoxia for the next 9 weeks. To assess intimal
obstruction, “the pulmonary artery occlusion index
(PAOI)” was developed to digitize all lesions. The small
pulmonary arteries were assessed by this index, and the
association between right ventricular systolic pressure
(RVSP) and PAOI was investigated. An endothelin
receptor antagonist, ambrisentan, was administered by
gavage to rats during either hypoxia (Prevention study
group, n=25) or normoxia (Early treatment group,
n=15). Results: PAOI showed a positive correlation with
RVSP, and both RVSP and PAOI increased gradually
over time. There were no severe occlusive lesions in
either group, but the density of partially occlusive
lesions was significantly decreased in the Prevention
study group. Conclusion: A novel PAOI index was
developed, and this index was strongly correlated with
RVSP. Furthermore, ambrisentan reduced luminal
occlusive lesions more effectively when treatment was
given during the first 2 weeks of hypoxia