Impaired coronary dilator responses to substance P and impaired flow-dependent dilator responses in heart transplant patients with graft vasculopathy.
OBJECTIVE
Because pathologic mechanisms for transplant vasculopathy are still uncertain, we tested the hypothesis that endothelial function, in terms of the release of endothelium-derived relaxing factor (EDRF), is impaired in patients with evidence of angiographic transplant vasculopathy.


BACKGROUND
The long-term prognosis after heart transplantation is mainly determined by the development of transplant vasculopathy.


METHODS
The study included 23 patients undergoing diagnostic cardiac catheterization approximately 40 months after heart transplantation. Patients were classified into those with (n = 8) and those without (n = 15) angiographic evidence of transplant vasculopathy. Coronary flow velocity (by intravascular Doppler echocardiography) and epicardial coronary diameter (by quantitative angiography) were determined after intracoronary bolus injections (1 ml) of the endothelium-dependent dilator substance P (20 pmol) and the endothelium-independent dilators nitroglycerin (0.1 mg) and papaverine (8 mg). Substances were injected through the lumen of the Doppler catheter, which was placed into the midportion of the left anterior descending artery.


RESULTS
Increases in blood flow velocity in response to substance P were significantly less in patients with than in patients without evidence of transplant vasculopathy. In addition, flow-mediated dilation of epicardial coronary arteries in response to papaverine was abolished in patients with such evidence. Vasodilation of epicardial coronary arteries in response to nitroglycerin and increases in flow velocity in response to papaverine were similar in both groups.


CONCLUSIONS
These results suggest that transplant vasculopathy in heart transplant patients is associated with endothelial dysfunction (that is, impaired EDRF-mediated vasodilation). Furthermore, responsiveness of epicardial arteries to increased flow appears to be abolished in patients with evidence of transplant vasculopathy. These abnormal vascular functions may contribute to the pathogenesis of transplant vasculopathy and its vascular complications.
Mügge
A
A
Division of Cardiology, Hannover Medical School, Germany.
Heublein
B
B
Kuhn
M
M
Nolte
C
C
Haverich
A
A
Warnecke
J
J
Forssmann
W G
WG
Lichtlen
P R
PR
D000328:Adult; D000704:Analysis of Variance; D001783:Blood Flow Velocity / Q000187:drug effects; D001792:Blood Platelets / Q000737:chemistry; D006328:Cardiac Catheterization; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects*; D006152:Cyclic GMP / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006083:Graft Occlusion, Vascular / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000503:physiopathology*; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D005996:Nitroglycerin / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D013373:Substance P; D010208:Papaverine; D005996:Nitroglycerin; D006152:Cyclic GMP