Macitentan treatment retards the progression of established pulmonary arterial hypertension in an animal model  I.P. Temple, O. Monfredi, G. Quigley,

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Macitentan treatment retards the progression of established pulmonary arterial hypertension in an animal model  I.P. Temple, O. Monfredi, G. Quigley, H. Schneider, M. Zi, E.J. Cartwright, M.R. Boyett, V.S. Mahadevan, G. Hart  International Journal of Cardiology  Volume 177, Issue 2, Pages 423-428 (December 2014) DOI: 10.1016/j.ijcard.2014.09.005 Copyright © 2014 The Authors Terms and Conditions

Fig. 1 Pulsed wave Doppler recording through the pulmonary artery and measurement of PVmax, PAAT and PAD. The x axis measures time and the y axis measures velocity. PAAT is the time from the beginning of flow to the peak velocity, measured from the x axis. PVmax is the maximum velocity measured from the y-axis. PAD is the gradient of the initial deceleration of the pulmonary velocity profile. International Journal of Cardiology 2014 177, 423-428DOI: (10.1016/j.ijcard.2014.09.005) Copyright © 2014 The Authors Terms and Conditions

Fig. 2 Echo images showing the development of pulmonary hypertension assessed by the pulmonary velocity profile. The profile has a typical ‘rounded’ shape prior to injection. At day 21 no change is seen in the CON animal but the MCT animal shows a change to a typical ‘spike and dome’ morphology with a reduced PAAT and increased PAD. The MACI animal has an intermediate profile between the two groups. International Journal of Cardiology 2014 177, 423-428DOI: (10.1016/j.ijcard.2014.09.005) Copyright © 2014 The Authors Terms and Conditions

Fig. 3 Development of pulmonary hypertension. Mean and SEM plotted at each time point. The MACI group was compared with the MCT group and the CON group by a t-test. Pulmonary hypertension developed in the MACI group by day 7 (i.e. before the initiation of macitentan) with a reduced PVmax. There is a significant improvement in the MACI group compared to the MCT group at day 14 and day 21 with a reduced PAD, right ventricular wall thickness in systole and QT interval and an increased pulmonary artery acceleration time. International Journal of Cardiology 2014 177, 423-428DOI: (10.1016/j.ijcard.2014.09.005) Copyright © 2014 The Authors Terms and Conditions

Fig. 4 Kaplan–Meir curves showing the freedom from symptomatic endpoints. The animals were sacrificed on the day they met their symptomatic endpoints. There is a significant difference between the CON and MACI treated groups (p=0.01) but no difference between the MACI treated and MCT groups (p=0.50). International Journal of Cardiology 2014 177, 423-428DOI: (10.1016/j.ijcard.2014.09.005) Copyright © 2014 The Authors Terms and Conditions