Circulation, Vol 84, 1984-1992, Copyright © 1991 by American Heart Association
AM Zeiher, H Drexler, H Wollschlager and H Just
BACKGROUND. The vascular endothelium is capable of regulating tissue
perfusion by the release of endothelium-derived relaxing factor to modulate
vasomotor tone of the resistance vasculature. METHODS AND RESULTS. To test
whether atherosclerosis is associated with a functional abnormality of
endothelium-mediated microvascular relaxation affecting coronary blood flow
regulation, we compared coronary blood flow responses with cold pressor
testing with the response of the coronary vasculature to acetylcholine (an
endothelium-dependent vasodilator) and to papaverin (a direct dilator of
vascular smooth muscle) in 12 normal control patients and in 19 patients
with non-flow- limiting epicardial atherosclerosis (CAD). The drugs were
subselectively infused into the left anterior descending coronary artery
via a Doppler catheter, and the response in coronary blood flow was
assessed by measuring intracoronary blood flow velocity and cross-
sectional arterial area (quantitative angiography). Coronary vascular
resistance decreased in all normal control patients by -24.1 +/- 5.5% (mean
+/- SD) during the cold pressor test, whereas the CAD patients demonstrated
a variable coronary vascular resistance response to cold pressor testing
despite comparable changes in the rate-pressure product. The slopes of the
acetylcholine dose-blood flow response (percent change in coronary blood
flow/dosage of acetylcholine) were significantly reduced in the CAD
patients with 38.5 +/- 24.8 compared with the normal patients (80.8 +/-
28.1; p less than 0.001). Although coronary blood flow responses to
papaverin were slightly but significantly (p less than 0.05) reduced in the
CAD patients, the response to the endothelium-dependent dilator
acetylcholine was considerably out of proportion to the papaverin response
in these patients compared with the normal patients. The capacity of the
coronary system to increase blood flow in response to acetylcholine
expressed as relative proportion of the maximal papaverin response was 52.5
+/- 18.2% in the normal control patients but only 33.6 +/- 23.6% in the CAD
patients (p less than 0.025 versus normals). There was a significant
negative correlation (r = -0.69; p less than 0.0001) between cold pressor
test-induced changes in coronary vascular resistance and the capacity of
the coronary system to increase blood flow in response to acetylcholine.
CONCLUSIONS. Early stages of epicardial atherosclerosis are associated with
an impairment in endothelium-dependent dilation of the coronary
microvasculature, indicating that the pathophysiological consequences of
atherosclerosis may extend into the human coronary microcirculation. The
correlation between cold pressor test-induced coronary vascular resistance
changes and the extent of endothelial dysfunction suggests a relation
between endothelial function of the microvasculature and coronary blood
flow regulation during sympathetic stimulation associated with increased
myocardial work.
ARTICLES
Endothelial dysfunction of the coronary microvasculature is associated with coronary blood flow regulation in patients with early atherosclerosis
Department of Cardiology, University of Freiburg, FRG.
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