Abstract
The aims of this study were: (1) to test whether oscillatory shear stress further exacerbates endothelial dysfunction in patients with moderate-severe COPD, and (2) to test whether low flow oxygen administration improves endothelial function and is protective against oscillatory shear stress-induced endothelial dysfunction in patients with moderate-severe COPD. In 17 patients and 10 age-matched non-smoking control subjects we examined brachial artery flow-mediated dilation (FMD) and circulating microparticles before and after 20 minutes of experimentally-induced oscillatory shear stress. COPD patients performed this intervention a second time following a 20-minute wash in period of low flow supplemental oxygen to normalize arterial oxygen saturation. COPD patients had ~six-fold greater baseline retrograde shear rate (P < 0.05) and lower FMD (P < 0.05). The oscillatory shear stress intervention induced significant decreases in brachial artery FMD of all groups (P < 0.05). Oscillatory shear stress elevated circulating markers of endothelial cell apoptosis (CD31+/CD41b− microparticles) in COPD patients, but not age-matched controls. Supplemental oxygen administration abrogated the oscillatory shear stress-induced increase in CD31+/CD41b− microparticles, and improved FMD after accounting for the shear stress stimulus. We have demonstrated that acutely disturbed blood flow with increased retrograde shear stress further deteriorates the already impaired endothelial function with attendant endothelial apoptosis in patients with moderate-severe COPD.
Highlights
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the lungs that exerts complications systemically, highlighted by an increased risk of cardiovascular disease
The only difference was that at baseline, oscillatory shear index (OSI) was only lower in controls compared to the COPD patients during O2 normalization – otherwise OSI was always lower in controls (P < 0.05), with OSI increasing in all groups following cuff inflation (P < 0.01)
There was a moderate correlation between baseline flow-mediated dilation (FMD) and retrograde shear in COPD patients (r = 0.573, P = 0.07) but no correlation was observed in controls (r = 0.009, P = 0.98)
Summary
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the lungs that exerts complications systemically, highlighted by an increased risk of cardiovascular disease. Patients with COPD present with elevated levels of circulating endothelial-derived microparticles (EMPs) and impaired flow-mediated dilation (FMD), indicating a pro-atherogenic endothelial cell phenotype; whether the endothelium of patients with COPD remains sensitive to oscillatory shear stress-induced dysfunction remains unknown. The magnitude and direction of shear stress exerted upon the endothelium mediates gene expression; laminar, pulsatile shear stress induces a quiescent endothelial cell phenotype that is anti-inflammatory, vasodilatory, and antithrombotic, whereas oscillatory, low time-averaged mean shear stress is pro-atherogenic[8]. Healthy humans indicate that 20–30 minutes of experimentally-induced oscillatory shear stress increases EMP markers of endothelial cell activation and apoptosis, and decreases FMD9,10. Acute hypoxemia increases circulating MPs, while superimposing oscillatory shear stress impairs FMD in young, healthy humans[11]. The primary aims of this study were two-fold: 1) to test whether oscillatory shear stress further exacerbates endothelial dysfunction in patients with COPD compared to age-matched controls, and 2) to test whether low flow oxygen administration, to alleviate hypoxemia, improves endothelial function and is protective against oscillatory shear stress-induced endothelial dysfunction in patients with COPD
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
