Key result
Right pneumonectomy in rats significantly increased mean pulmonary arterial pressure to 35 mmHg compared to 18 mmHg in sham surgery at 28 days (P=0.001).
Why the study?
Pulmonary hypertension and heart disease contribute to high morbidity after pneumonectomy, but the underlying pathophysiology remains poorly understood.
Does right pneumonectomy induce pulmonary hypertension and right heart remodeling in rats, and does shear stress alter pulmonary endothelial paracrine control of SMC growth?
RCT (n=60)
randomly
Does right pneumonectomy induce pulmonary hypertension and right heart remodeling in rats, and does shear stress alter pulmonary endothelial paracrine control of SMC growth?
Absolute Event Rate: 35% vs 18%
p-value: p=0.001
Right pneumonectomy in rats induces pulmonary hypertension and right heart remodeling, likely driven by shear stress altering pulmonary endothelial paracrine control of smooth muscle cell growth.
Rat pneumonectomy model induces pulmonary hypertension; leaves open human translation and mechanistic validation.
OBJECTIVES: Pulmonary hypertension and heart disease contribute to the high morbidity rate following pneumonectomy (PN). The pathophysiology is still poorly understood. The objective was to investigate the consequences of PN on cardiopulmonary function in rats and to explore in vitro the involved mechanisms. METHODS: Sixty Sprague-Dawley male rats randomly underwent either a right PN (PN group) or sham surgery. Ten rats per group were sacrificed on postoperative days 3, 7 and 28. Cardiopulmonary alterations were investigated by echocardiographic, haemodynamic and histological analyses. In vitro, the shear stress was reproduced using a Flexcell Tension™ cyclic stretch on cultured human pulmonary endothelial cells (P-ECs) to investigate the impact on pulmonary artery smooth muscle cell (PA-SMC) growth. Data are expressed as mean ± SD. RESULTS: Mean pulmonary arterial pressure gradually increased in the PN group to reach 35 ± 7 mmHg on postoperative day 28 vs 18 ± 4 in sham (P = 0.001), likewise the proportion of muscularized distal pulmonary arteries, 83 ± 1% vs 5 ± 1%, respectively (P < 0.001), related to in situ PA-SMC proliferation. The right ventricle area and lateral wall thickness were doubled in the PN group on postoperative day 28. The left ventricle ejection fraction decreased on postoperative days 7 and 28 while the right ventricle function was maintained. In vitro, the human PA-SMC growth was significantly greater when seeded with stretched vs non-stretched P-EC media, highlighting the role of shear stress on the P-EC paracrine function. CONCLUSIONS: Right PN led to pulmonary hypertension and proportional right heart remodelling in rats. The shear stress related to high blood flow alters the pulmonary endothelial paracrine control of SMC growth.
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Sentenac et al. (2020) conducted an RCT in Pulmonary hypertension after pneumonectomy (n=60). Right pneumonectomy vs. Sham surgery was evaluated on Mean pulmonary arterial pressure on postoperative day 28 (p=0.001). Right pneumonectomy in rats significantly increased mean pulmonary arterial pressure to 35 mmHg compared to 18 mmHg in sham surgery at 28 days (P=0.001).
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