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Dose Response Relationship in a Monocrotaline Rat Model of Pulmonary Hypertension
Author(s) -
Porvasnik Stacy Lynn,
Embury Jennifer E.,
Byrne Barry J.,
Spencer Carolyn T.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1186
Subject(s) - histology , medicine , hemodynamics , pulmonary hypertension , edema , lung , body weight , blood pressure , cardiology , gastroenterology
Monocrotaline (MCT) is a toxic alkaloid that causes endothelial cell damage and lung injury resulting in pulmonary vascular remodeling and pulmonary hypertension (PH) in rats. Previous studies reported varying doses of MCT and body weight. We have now evaluated dose‐response relationships in rats at varied initial body weights: (A=130–150 g; B=200–250 g; C=300–340 g) and 4 doses of MCT (40, 60, 80, 100 mg/kg). Outcome measures at 4 weeks post MCT included change in body weight, hemodynamics, morphological analysis and histology. The results showed that within each weight group the peak and mean PA pressure and PA:LV pressure ratio was significantly different than controls. Peak PA pressure was significantly different between groups B and C with doses 40 and 80 mg/kg (p=0.047 and p=0.002) respectively. Group C showed statistical significance between the 100 mg/kg when compared to the other 3 doses. Histology scores correlated directly with peak and mean PA pressure (r=0.47 for arterial wall thickening and r=0.61 for alveolar edema). An increased mortality was seen between weeks 3–4 in lower body weight groups (group A=83%, group B= 9%, group C= 2% mortality), necessitating obtaining new data at 3 weeks in group A. Liver histology results are pending. This study demonstrates a dose‐response relationship between MCT, pulmonary hemodynamics and histology over an expanded dose initial weight range.