Single intraperitoneal injection of monocrotaline as a novel large animal model of chronic pulmonary hypertension in Tibet minipigs.
OBJECTIVE
The purpose of this study was to establish an animal model of chronic pulmonary hypertension with a single-dose intraperitoneal injection of monocrotaline (MCT) in young Tibet minipigs, so as to enable both invasive and noninvasive measurements and hence facilitate future studies.


METHODS
Twenty-four minipigs (8-week-old) were randomized to receive single-dose injection of 12.0 mg/kg MCT (MCT group, n = 12) or placebo (control group, n = 12 each). On day 42, all animals were evaluated for pulmonary hypertension with conventional transthoracic echocardiography, right heart catheterization (RHC), and pathological changes. Findings of these studies were compared between the two groups.


RESULTS
At echocardiography, the MCT group showed significantly higher pulmonary arterial mean pressure (PAMP) compared with the controls (P<0.001). The pulmonary valve curve showed v-shaped signals with reduction of a-waves in minipigs treated with MCT. In addition, the MCT group had longer pulmonary artery pre-ejection phases, and shorter acceleration time and ejection time. RHC revealed higher mean pulmonary arterial pressure (mPAP) in the MCT group than in the control group (P<0.01). A significant and positive correlation between the mPAP values and the PAMP values (R = 0.974, P<0.0001), and a negative correlation between the mPAP and ejection time (R = 0.680, P<0.0001) was noted. Pathology demonstrated evidence of pulmonary vascular remodeling and higer index of right ventricular hypertrophy in MCT-treated minipigs.


CONCLUSIONS
A chronic pulmonary hypertension model can be successfully established in young minipigs at six weeks after MCT injection. These minipig models exhibited features of pulmonary arterial hypertension that can be evaluated by both invasive (RHC) and noninvasive (echocardiography) measurements, and may be used as an easy and stable tool for future studies on pulmonary hypertension.
First Affiliated Hospital, Guangzhou Medical University; Guangzhou, Guangdong, China ; State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, Guangdong, China.
Guang-qiao
GQ
Zeng
Rong
R
Liu
Hai-xing
HX
Liao
Xin-feng
XF
Zhang
Yuan-xin
YX
Qian
Bao-hua
BH
Liu
Qing-hong
QH
Wu
Jin
J
Zhao
Wei-wang
WW
Gu
Hong-tao
HT
Li
D000818:Animals; D004195:Disease Models, Animal; D004452:Echocardiography; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000503:physiopathology; D016686:Monocrotaline / Q000633:toxicity*; D011651:Pulmonary Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D013552:Swine; D013556:Swine, Miniature
D016686:Monocrotaline