Circulation, Vol 86, 1156-1164, Copyright © 1992 by American Heart Association
CB Treasure, JA Vita, P Ganz, TJ Ryan Jr, FJ Schoen, VI Vekshtein, AC Yeung, GH Mudge, RW Alexander and AP Selwyn
BACKGROUND. The coronary arteries of transplanted hearts frequently develop
accelerated diffuse arteriosclerosis. The effects of this disease on
resistance vessel function are unknown. METHODS AND RESULTS. To investigate
the integrity of endothelium-dependent small-vessel vasodilation in
transplanted hearts, coronary blood flow (CBF) responses to the
endothelium-dependent dilator acetylcholine (10(-8) to 10(-6) M) and the
essentially endothelium-independent dilator adenosine (10(-6) to 10(-4) M)
were assessed in 40 studies of 29 transplant patients 1-3 years after
transplantation and in seven nontransplanted controls. CBF was measured at
constant arterial pressure with a Doppler catheter in the left anterior
descending coronary artery. Controls, year 1 transplant patients, and year
2 transplant patients had similar increases in CBF in response to
acetylcholine (232 +/- 40%, 200 +/- 41%, and 201 +/- 54%, respectively; p =
NS), whereas year 3 transplant patients had increased CBF of only 100 +/-
39% (p less than 0.05 versus controls). An index of the proportion of CBF
reserve attributable to endothelium-dependent dilation was obtained by
normalizing each patient's peak acetylcholine flow response by the peak
adenosine flow response. In patients receiving both acetylcholine and
adenosine, endothelium-dependent flow responses declined over time [57 +/-
9% in controls, 56 +/- 10% for year 1, 47 +/- 12% for year 2, and 29 +/- 9%
for year 3 (p less than 0.05 versus controls)]. An increased mean
cyclosporine level (range, 99-261 ng/ml) (r = 0.67, p = 0.004) and
increased transplant recipient age (range, 20-63 years) (r = 0.51, p =
0.004) predicted a preserved endothelium-dependent microvascular response.
CONCLUSIONS. Thus, microvascular endothelium-dependent dilation
deteriorates over time in the transplanted heart, which may reflect
underlying graft arteriosclerosis and contribute to ischemic damage of the
myocardium.
ARTICLES
Loss of the coronary microvascular response to acetylcholine in cardiac transplant patients
Department of Medicine (Cardiovascular Division), Brigham and Women's Hospital, Boston, MA 02115.
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