Metformin prevents the development of monocrotaline‑induced pulmonary hypertension by decreasing serum levels of big endothelin‑1

Figures

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  Figure 1. Representative echocardiogram images of right heart functional evaluation. (A-D) Representative images of the (A) eccentricity index from the parasternal short axis view, (B) MPA/Ao in the short-axis view at the aorta level, (C) TAPSE in the apical four-chamber view and (D) RV Tei index using the Dual Doppler system in the right parasternal RV outflow view. (E) Peak transtricuspid early diastolic wave velocity and tissue Doppler tricuspid annular velocities at systole and at early diastole were measured using the Dual Doppler system in the apical four-chamber view. Ao, aortic diameter; ET, ejection time; ICT, isovolumetric contraction time; IRT, isovolumetric relaxation time; LA, left atrium; LV, left ventricle; MPA, main pulmonary artery; PA, pulmonary artery; RA, right atrium; RV, right ventricle; TAPSE, tricuspid annular plane systolic excursion by M-mode imaging; TV, tricuspid valve.

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  Figure 2. Blood pressure and pulmonary arterial pressure measurements in vivo. Measurements of (A) SBP, (B) MBP, (C) DBP, (D) SPAP, (E) MPAP and (F) DPAP in the sham group (n=9), MT group (n=8) and PH group (n=10). Horizontal lines represent the median for each group. *P<0.05. DBP, diastolic blood pressure; DPAP, diastolic pulmonary artery pressure; MBP, mean blood pressure; MPAP, mean pulmonary artery pressure; MT, metformin treatment; PH, pulmonary hypertension; SBP, systolic blood pressure; SPAP, systolic pulmonary artery pressure.

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  Figure 3. Histopathological analysis of pulmonary arterial remodeling four week after MCT injection. Hematoxylin & eosin staining of the (A) small pulmonary artery (50-200 µm in diameter; magnification, x400) and (B) lung stroma cells (magnification, x400) in the sham group (n=9), MT group (n=8) and PH group (n=10). (C) Quantification of MWT and WA of pulmonary arteries from (A) and (B). Data are presented as mean ± SD; *P<0.05. MT, metformin treatment; MWT, medial wall thickness; PH, pulmonary hypertension; WA, wall area.

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  Figure 4. Evaluation of pulmonary artery flow. (A) Echocardiograph images of AT/ET in the sham group (n=9), MT group (n=8) and PH group (n=10). (B) Traces of the above images presented in (A). The images demonstrate the short flow AT in the MT and PH groups, and the flow reversal in the deceleration phase of pulmonary artery flow in the PH group (yellow arrow head). (C) AT/ET of pulmonary artery flow in each group. Each point represents an individual and the horizontal lines represent the median for each group; *P<0.05. AT, acceleration time; ET, ejection time; MT, metformin treatment; PH, pulmonary hypertension.

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  Figure 5. ELISA measured serum big ET-1 levels. Big ET-1 levels were determined in the sham (n=9), MT (n=8) and PH group (n=10). Data are presented as mean ± SD; *P<0.05. ET-1, endothelin-1; MT, metformin treatment; PH, pulmonary hypertension.