Abstract
BackgroundThe outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function.MethodsSaline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14–28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis.ResultsThe treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71 ± 0.05 for MCT group to 0.50 ± 0.06 for MCT + NAC group, p < 0.05). Right ventricular function was also improved with NAC treatment associated with a significant decrease in cardiomyocyte hypertrophy (625 ± 69 vs. 439 ± 21 μm2 for MCT and MCT + NAC group respectively, p < 0.001) and heart fibrosis (14.1 ± 0.8 vs. 8.8 ± 0.1% for MCT and MCT + NAC group respectively, p < 0.001).ConclusionsThrough its immuno-modulatory and cardioprotective properties, NAC has beneficial effect on pulmonary vascular and right heart function in experimental PH.
Highlights
Pulmonary arterial hypertension (PAH) is a rare condition characterised by small pulmonary artery remodeling, leading to chronic pre-capillary pulmonary hypertension (PH), elevated pulmonary vascular resistance and right heart failure [1]
NAC improves cardiac function and decreases pulmonary vascular remodeling in MCT-induced PH with no effect on systemic pressure Rats exposed to MCT consistently developed significant PH at day 28, with an increase of right ventricular systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP), a fall of cardiac output (CO) associated with high Total pulmonary resistance (TPR)
Right ventricular hypertrophy assessed by the right ventricle (RV)/(LV+S) ratio was increased after MCT exposure due to pressure overload
Summary
Pulmonary arterial hypertension (PAH) is a rare condition characterised by small pulmonary artery remodeling, leading to chronic pre-capillary pulmonary hypertension (PH) (mean pulmonary artery pressure above 25 mmHg and mean pulmonary artery wedge pressure below 15 mmHg), elevated pulmonary vascular resistance and right heart failure [1]. Pulmonary vascular remodeling promotes elevation of pulmonary vascular resistance leading to right ventricular hypertrophy characterized by cardiomyocyte hypertrophy and extracellular matrix changes with fibrosis. Oxidative stress was speculated to play a role in the pathophysiology of human and experimental PH [17,18,19,20]. Markers of oxidative stress were found in pulmonary vascular lesions of PAH patients [21] and urinary isoprostanes have recently been shown to independently correlate with survival [22]. We hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
