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Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans
D A Cox1, J A Vita, C B Treasure
1Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Insights
Large coronary arteries in humans dilate with increased blood flow, a response impaired by atherosclerosis. This study investigated flow-mediated dilation in healthy and diseased arteries, finding significant impairment in those with atherosclerosis.
Area of Science:
- Cardiovascular Physiology
- Vascular Biology
- Atherosclerosis Research
Background:
- Endothelium-dependent vasodilation is crucial for regulating blood flow.
- Atherosclerosis is known to impair vascular function, including vasodilation.
- Animal studies suggest flow-induced dilation is endothelium-dependent.
Purpose of the Study:
- To determine if human coronary arteries exhibit flow-mediated dilation.
- To test if atherosclerosis impairs this flow-mediated dilation response.
- To investigate the role of the endothelium in coronary artery vasodilation.
Main Methods:
- Adenosine infusion into the left anterior descending (LAD) coronary artery to increase blood flow.
- Measuring proximal LAD diameter changes in response to flow changes.
- Comparing flow-mediated dilation in patients with smooth LAD segments versus those with mild atherosclerosis.
Main Results:
- Adenosine infusion increased coronary blood flow in a dose-dependent manner.
- Patients with smooth LAD segments showed significant flow-mediated dilation (+13.2%).
- Patients with mild atherosclerosis showed no significant flow-mediated dilation (+1.8%), despite higher flow increases.
Conclusions:
- Human large coronary arteries exhibit flow-mediated dilation.
- This flow-mediated dilation is significantly impaired in the presence of mild atherosclerosis.
- Endothelial dysfunction in atherosclerosis limits the ability of coronary arteries to dilate in response to increased blood flow.
Abstract:
Studies in animals have suggested that increases in blood flow result in dilation of large arteries by an endothelium-dependent mechanism. Atherosclerosis can impair endothelium-dependent vasodilation to vasoactive agents. The purpose of this study was to determine whether or not large coronary arteries in humans exhibit dilation with increases in blood flow and to test the hypothesis that this response is impaired in the presence of atherosclerosis. Graded concentrations of adenosine were infused into the distal left anterior descending (LAD) coronary artery to test the dilator response of the proximal LAD to increases in blood flow. The proximal LAD was thereby exposed to changes in blood flow, but not directly to adenosine. Ten patients with angiographically smooth proximal LAD segments (group 1) and seven patients with irregularities in the proximal LAD consistent with mild atherosclerosis (group 2) were studied. Infusions of adenosine throughout the range of 0.022 to 2.2 mg/min into the LAD produced a dose-dependent increase in estimated coronary blood flow and a mean increase of 305 +/- 27% at 2.2 mg/min adenosine. At 2.2 mg/min adenosine, a striking difference (p less than 0.001) occurred between the significant flow-mediated dilation of the proximal LAD observed in group 1 (+13.2 +/- 1.3% from 2.63 +/- 0.16 mm, p less than 0.001), and the lack of dilation in group 2 (+1.8 +/- 1.5% from 3.20 +/- 0.17 mm, p = NS), despite a greater increase in coronary blood flow in group 2 (+387 +/- 29%) than in group 1 (+230 +/- 36%).(ABSTRACT TRUNCATED AT 250 WORDS)