Hemodynamic and Histopathologic Benefits of Early Treatment with Macitentan in a Rat Model of Pulmonary Arterial Hypertension
Korean Circulation Journal
;
: 839-853, 2018.
Artículo
en Inglés
| WPRIM
| ID: wpr-738746
ABSTRACT
BACKGROUND AND OBJECTIVES:
Macitentan (MAC) reduces morbidity and mortality among advanced-stage pulmonary arterial hypertension (PAH) patients. However, data regarding the histopathologic and hemodynamic benefits of MAC treatment at an early stage of PAH is lacking.METHODS:
One week after monocrotaline (MCT) injection, rats were randomly assigned to MAC (n=16), MAC combined with sildenafil (SIL) (MAC+SIL, n=16), or normal saline (MCT, n=16). Twelve sham rats (Sham) were included for comparison. Right ventricular (RV) systolic function was assessed via echocardiography as the RV fractional area change (RV-FAC). An invasive pressure-volume analysis using a Millar conductance catheter was performed 7 weeks after MCT injection. Rats were subsequently euthanized for histopathologic analysis.RESULTS:
RV-right atrial pressure gradient on echocardiography was significantly increased 3 weeks after MCT injection, but was maintained in the Sham. RV-FAC was less deteriorated in the MAC, compared to that in the MCT (44±3% vs. 25±7%, p 0.05 vs. the MAC). On invasive hemodynamic analyses, RV end-systolic (196±78 µL) and end-diastolic volumes (310±86 µL), pulmonary artery systolic pressure (89±7.2 mmHg), and end-systolic pressure-volume relationship (−254±25.1) were significantly worse in the MCT vs. in the MAC (101±45 µL, 235±55 µL, 40±10.5 mmHg, and −145±42.1, respectively) and MAC+SIL (109±47 µL, 242±46 µL, 38±9.2 mmHg, and −151±39.2, respectively) (all p 0.05). On histopathology, both RV and lung fibrosis were significantly reduced in the MAC and MAC+SIL vs. in the MCT (all p < 0.05); the 2 treatment groups did not differ.CONCLUSIONS:
MAC treatment at an earlier stage significantly attenuated experimental PAH progression hemodynamically and histopathologically.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Patología
/
Arteria Pulmonar
/
Presión Sanguínea
/
Fibrosis
/
Ecocardiografía
/
Mortalidad
/
Monocrotalina
/
Modelos Animales
/
Catéteres
/
Presión Atrial
Tipo de estudio:
Estudio pronóstico
Límite:
Animales
/
Humanos
Idioma:
Inglés
Revista:
Korean Circulation Journal
Año:
2018
Tipo del documento:
Artículo
Similares
MEDLINE
...
LILACS
LIS