Pulmonary Vascular Disease |

Rapamycin Improves Vascular Remodeling in Monocrotaline Induced Pulmonary Hypertension FREE TO VIEW

Aysun Sengul; Cigdem Vural; Sertan Arkan; Cuneyt Ozer; Aysegul Tas; Busra Yaprak; Olcay Bildirici
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Kocaeli Derince Education and Research Hospital, Kocaeli, Turkey

Chest. 2014;146(4_MeetingAbstracts):843A. doi:10.1378/chest.1988841
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SESSION TITLE: DVT/PE/Pulmonary Hypertension Posters III

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: Pulmonary hypertension is a serious disease, characterized by progressive elevation of pulmonary arterial resistance, leading to right ventricular failure and death. Abnormal vasoconstriction of pulmonary arterioles caused by vascular endothelial injury and/or remodeling of smooth muscle cell including proliferation and hypertrophy appear to be primary factors. We aimed to evaluate the effect of rapamycin (RAPA), a potent cell cycle inhibitor, on exercise capacity, right ventricle hypertrophy and pulmonary vascular remodelling.

METHODS: 9-week-old male Wistar rats (160-240g) were randomly divided into three groups: untreated animals (controls, n = 7), monocrotaline (MCT) only (MCT, 60 mg/kg administered subcutaneously on day 1 of the study period, n = 6), and MCT plus RAPA group (MCT, 60 mg/kg administered subcutaneously on day 1 of the study period and RAPA, 3 mg/kg, administered daily by orally from day 21 until the end of the study period, n = 7).Five weeks after MCT administration, exercise testing was performed in all study animals by using forced swimming test. At the end of the experiment, rats were sacrificed under light ether anesthesia. Hearts and lungs were removed and right ventricular hypertrophy and pulmonary vascular remodeling were analyzed.

RESULTS: At the 35th day, mortality rates for groups control, MCT, MCT+RAPA were 0%, 33.3%, 42.8%, respectively. Application of RAPA in MCT-treated animals didn’t improve to exercise capacity compared to the MCT group. Although there were not significant differences between MCT and MCT+RAPA group (p=0.66), RV hypertrophy was lower in the MCT+RAPA group. A significant variance was found in the wall thickness of medium-sized pulmonary arteries between MCT and MCT+RAPA groups (p=0.04). There was also a significant variance in the number (per optical field) of muscularized pulmonary arterioles between MCT and MCT+ RAPA group (p=0.02).

CONCLUSIONS: Rapamycin may be a novel therapy for antiremodelling treatment in pulmonary hypertension.Larger sample size studies are needed to confirm our findings.

CLINICAL IMPLICATIONS: Pulmonary hypertension is a progressive disease that is not curable with the currently therapies. We think rapamycin could reverse vascular remodelling in pulmonary hypertension.

DISCLOSURE: The following authors have nothing to disclose: Aysun Sengul, Cigdem Vural, Sertan Arkan, Cuneyt Ozer, Aysegul Tas, Busra Yaprak, Olcay Bildirici

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