title: Loss of the coronary microvascular response to acetylcholine in cardiac transplant patients.
abstract: BACKGROUND
  The coronary arteries of transplanted hearts frequently develop accelerated diffuse arteriosclerosis. The effects of this disease on resistance vessel function are unknown.
  
  
  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.
authors.affiliation: Department of Medicine (Cardiovascular Division), Brigham and Women's Hospital, Boston, MA 02115.
authors.forename: C B
authors.initials: CB
authors.lastname: Treasure
authors.forename: J A
authors.initials: JA
authors.lastname: Vita
authors.forename: P
authors.initials: P
authors.lastname: Ganz
authors.forename: T J
authors.initials: TJ
authors.lastname: Ryan
authors.forename: F J
authors.initials: FJ
authors.lastname: Schoen
authors.forename: V I
authors.initials: VI
authors.lastname: Vekshtein
authors.forename: A C
authors.initials: AC
authors.lastname: Yeung
authors.forename: G H
authors.initials: GH
authors.lastname: Mudge
authors.forename: R W
authors.initials: RW
authors.lastname: Alexander
authors.forename: A P
authors.initials: AP
authors.lastname: Selwyn
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology; D000328:Adult; D003326:Coronary Circulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005544:Forecasting; D016027:Heart Transplantation; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D010496:Pericardium; D011184:Postoperative Period
chemical_list: D000241:Adenosine; D000109:Acetylcholine