Time course of endothelial function in epicardial conduit coronary arteries and in the microcirculation in the long-term follow-up after cardiac transplantation

Background: Endothelial dysfunction has been reported in epicardial conduit coronary arteries and in the microcirculation after cardiac transplantation. It has been assumed that endothelial dysfunction may precede hemodynamically relevant transplant vasculopathy. In this study the long-term course of endothelial function was investigated in conduit coronary arteries and in the microcirculation after cardiac transplantation. Methods: Patients were stratified according to time after transplantation (group I, up to 2 years after transplantation; group II, 2 to 4 years after transplantation; group III, more than 4 years after transplantation). Changes of the diameter of proximal, mid and distal segments of the left anterior descending coronary artery and the circumflex branch of the left coronary artery were investigated after endothelium-dependent and endothelium-independent stimulation with acetylcholine (ACh, 50 and 100 μg i.c.) and nitroglycerin 0.3 mg i.c. Coronary flow changes were assessed endothelium-dependently (ACh 50 and 100 μg i.c.) and endothelium-independently (dipyridamole 0.56 mg/kg i.v.) utilizing an 8 F Judkins-style Doppler catheter. Results: Application of 50 μg/100 μg ACh resulted in a reduction of coronary artery diameter in proximal, mid and distal vascular segments of the left anterior descending coronary artery and the circumflex branch of the left coronary artery. The vasoconstrictive effect did not differ significantly between groups I,II and III. Nitroglycerin 0.3 mg i.c. increased coronary artery diameters in groups I, II and HI. ACh (50 μg/100 /gmg) increased coronary flow index by 217 ± 70%/236 ± 110% (P < 0.05 vs. baseline) in group I, 113 ± 26%/77 ± 22% (P < 0.05 vs. baseline) in group II and 108 ± 26%/109 ± 21% (P < 0.05 vs. baseline) in group III. Dipyridamole increased coronary flow index by 296 ± 78% (P < 0.05 vs. baseline) in group I, by 63 ± 16% (P < 0.05 vs. baseline and vs. group I) in group II and by 113 ± 30% (P < 0.05 vs. baseline and vs. group I) in group III. Conclusion: A constant vasosonstrictor response to ACh was observed in epicardial coronary arteries after cardiac transplantation indicating endothelial dysfunction independent of the time course. Endothelial dysfunction in these vessels may not be an early indicator of hemodynamically relevant transplant vasculopathy. Endothelium-dependent and endothelium-independent flow reserves decreased 2 years after transplantation and remained constant thereafter.