Coronary endothelial function in cardiac transplant recipients with accelerated coronary disease.
BACKGROUND
Previous studies with the endothelium-dependent vasodilator substance P have shown a preserved vasodilator response in cardiac transplant recipients with angiographically normal coronary arteries. Although endothelial dysfunction is known to occur in cardiac transplant recipients with accelerated coronary disease, the degree to which the endothelium is affected is not known precisely. The aim of the present study was to examine endothelial function in accelerated coronary disease following cardiac transplantation.


METHODS
Thirteen cardiac transplant recipients with epicardial coronary disease underwent substance P infusion. The response to incremental doses of substance P was measured in smooth segments of affected coronary arteries. Substance P was infused over 2 min with a starting dose of 1.4 pmol/min and a maximum of 22.4 pmol/min, reached by doubling the dose in steps, followed by an infusion of 2 mg isosorbide dinitrate over 2 min.


RESULTS
Substance P caused less vasodilation at lower concentrations, with a significantly higher dose required to achieve half maximal dilation compared with cardiac transplant recipients with no coronary disease. The mean maximal dilatation achieved with substance P was 22.98 +/- 4.62% compared to 21.95 +/- 4.9% with isosorbide dinitrate; the latter value was not significantly different from the maximal dilation achieved in cardiac transplant recipients without coronary disease.


CONCLUSIONS
In cardiac transplant recipients with accelerated coronary disease the functional vasodilatory ability of the coronary endothelium is impaired in segments of apparently unaffected epicardial arteries, which may lead to an increase in the resting vasoconstrictor tone and have important functional and therapeutic implications.
Kushwaha
S S
SS
Department of Cardiology, Harefield Hospital, Middlesex, UK.
Bustami
M
M
Lythall
D A
DA
Barbir
M
M
Mitchell
A G
AG
Yacoub
M H
MH
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D017023:Coronary Angiography; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000502:physiology
D013373:Substance P; D007548:Isosorbide Dinitrate