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논문 기본 정보

자료유형
학술저널
저자정보
Kyung-Hee Kim (Seoul National University College of Medicine) Hyung-Kwan Kim (Seoul National University College of Medicine) Stephen Y. Chan (University of Pittsburgh School of Medicine) Yong-Jin Kim (Seoul National University College of Medicine) Dae-Won Sohn (Seoul National University College of Medicine)
저널정보
대한심장학회 Korean Circulation Journal Korean Circulation Journal Vol.48 No.9
발행연도
2018.1
수록면
839 - 853 (15page)

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Background and Objectives Macitentan (MAC) reduces morbidity and mortality among advanced-stage pulmonary arterial hypertension (PAH) patients. However, data regarding the histopathologic and hemodynamic benefits of MAC treatment at an early stage of PAH is lacking. Methods One week after monocrotaline (MCT) injection, rats were randomly assigned to MAC (n=16), MAC combined with sildenafil (SIL) (MAC+SIL, n=16), or normal saline (MCT, n=16). Twelve sham rats (Sham) were included for comparison. Right ventricular (RV) systolic function was assessed via echocardiography as the RV fractional area change (RV-FAC). An invasive pressure-volume analysis using a Millar conductance catheter was performed 7 weeks after MCT injection. Rats were subsequently euthanized for histopathologic analysis. Results RV-right atrial pressure gradient on echocardiography was significantly increased 3 weeks after MCT injection, but was maintained in the Sham. RV-FAC was less deteriorated in the MAC, compared to that in the MCT (44±3% vs. 25±7%, p<0.05), and the co-administration of SIL showed no additional benefit (45±8%, p>0.05 vs. the MAC). On invasive hemodynamic analyses, RV end-systolic (196±78 µL) and end-diastolic volumes (310±86 µL), pulmonary artery systolic pressure (89±7.2 mmHg), and end-systolic pressure-volume relationship (−254±25.1) were significantly worse in the MCT vs. in the MAC (101±45 µL, 235±55 µL, 40±10.5 mmHg, and −145±42.1, respectively) and MAC+SIL (109±47 µL, 242±46 µL, 38±9.2 mmHg, and −151±39.2, respectively) (all p<0.05). However, the MAC and MAC+SIL did not differ (all p>0.05). On histopathology, both RV and lung fibrosis were significantly reduced in the MAC and MAC+SIL vs. in the MCT (all p<0.05); the 2 treatment groups did not differ. Conclusions MAC treatment at an earlier stage significantly attenuated experimental PAH progression hemodynamically and histopathologically.

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참고문헌 (24)

참고문헌 신청
Galie N / 2016 / 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT) / Eur Heart J 37:67~119 Crossref Humbert M / 2010 / Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era / Circulation 122:156~163 Crossref Schermuly RT / 2011 / Mechanisms of disease: pulmonary arterial hypertension / Nat Rev Cardiol 8:443~455 Crossref Nogueira-Ferreira R / 2015 / Exploring the monocrotaline animal model for the study of pulmonary arterial hypertension: a network approach / Pulm Pharmacol Ther 35:8~16 Crossref Galie N / 2008 / Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial / Lancet 371:2093~2100 Crossref

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