Profound lung remodeling in heart failure, a poorly understood phenomenon with a significant impact (715.6)

Abstract

Exercise intolerance, characterized by dyspnea and early onset of exertional fatigue, is a chief complaint among patients with heart failure (HF). Limb muscle dysfunction is a known contributor to exercise intolerance, however, this phenomena does not explain dyspnea. Lung remodeling has been reported in end‐stage HF patients which could contribute to dyspnea and exercise intolerance, underscoring the importance and urgent need to better understand its role in HF. Our aim is to characterize the development of lung remodeling and its impact on exercise intolerance in HF. We hypothesize that lung remodeling occurs early in the development of HF, causing exercise‐induced hemoglobin (Hb) desaturation, affecting exercise performance. Methods: Male CD1 mice were subject to either transverse aortic constriction (TAC) or sham surgery. Exercise tolerance and Hb saturation were measured during a graded exercise test. The animals were sacrificed and lungs excised and fixed for histological evaluation. Results: Time to exhaustion was decreased by 40% in TAC. Hb saturation in TAC decreased during exercise while sham remained unchanged (p<0.05). Hb levels were similar between sham and TAC animals. Lung compliance was significantly reduced in 9 week TAC compared to sham (p<0.05), which further declined by 18 weeks (p<0.01). Histological assessment revealed significant remodeling including a 43% increase in fibrosis (p<0.01), marked inflammation and distended alveoli. Conclusions: Lung remodeling plays a significant yet under acknowledged role in exercise intolerance in HF patients. Grant Funding Source: Ontario Thoracic Society