Pulmonary Disease, Chronic Obstructive Clinical Trial
Official title:
Regulation of Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease: A Mechanistic Approach
More patients with chronic obstructive pulmonary disease (COPD) die from cardiovascular disease than direct pulmonary complications. Inflammation and oxidative stress, characteristic in COPD, are likely contributors to the reduction in nitric oxide (NO) bioavailability and vascular endothelial dysfunction in COPD patients; however, this has yet to be determined. Thus, the overall objective of this proposal is to identify the role of NO bioavailability in contributing to vascular endothelial dysfunction in patients with COPD and to provide insight into the molecular mechanisms involved. Our central hypothesis is that inflammation and oxidative stress, both independently, contribute to the reduction in NO bioavailability and vascular endothelial dysfunction in patients with COPD.
Flow-Mediated Dilation (FMD) - Subjects will lie in the supine position for 20 minutes to
obtain hemodynamic steady state. A blood pressure cuff (Hokanson) will be placed around the
forearm (distal to the Doppler transducer) and rapidly inflated to 250 mmHg for 5 minutes
(circulatory arrest). Simultaneous ultrasound images of the vessel (B-mode) and Doppler
waveforms will be collected 10 seconds prior to and for 2 minutes following deflation of the
cuff. All B-mode images will be analyzed using automated edge detection software (Medical
Imaging Applications), while intensity weighted velocity spectra segments will be saved to
the GE Logiq 7 hard drive for off-line blood velocity waveform analysis. P.I. has utilized
the traditional method of brachial artery flow-mediated dilation (FMD) induced by reactive
hyperemia to assess vascular endothelial function in populations ranging from young healthy
adults to older adults with pathological conditions.
Spygmocor - Pulse Wave Velocity (PWV) - A Spygmocor® device will be used at baseline and
following each protocol to assess PWV. PWV analysis provides a non-invasive assessment of
arterial stiffness. Increased arterial stiffness is known to be associated with
cardiovascular disease. The participant is required to lie in a resting position for
approximately 30-45 minutes. The research assistant will place ECG electrode sensors at the
carotid, femoral, radial and distal artery locations. A highly sensitive pen-like device,
called a tonometer, is then gently applied to record the velocity of the blood flow between
each of the points.
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