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Endothelium-dependent responses in long-term human coronary artery bypass grafts
D D Ku1, J B Caulfield, J K Kirklin
1Department of Pharmacology, University of Alabama, Birmingham 35294.
Insights
Long-term transplanted human coronary artery bypass grafts (CABGs) retain endothelium-dependent responses. Intimal proliferative lesions, not graft duration, significantly alter graft reactivity.
Area of Science:
- Vascular Biology
- Transplantation Immunology
- Cardiovascular Surgery
Background:
- Long-term patency of coronary artery bypass grafts (CABGs) is crucial for cardiac transplant recipients.
- Understanding graft reactivity to vasodilators is essential for managing graft function.
Purpose of the Study:
- To investigate the endothelium-dependent and independent responses of long-term human CABGs.
- To determine the impact of graft duration and intimal proliferative lesions on graft reactivity.
Main Methods:
- Human CABG segments (n=109) from 14 cardiac transplant patients were studied in vitro.
- Graft responses to acetylcholine, calcium ionophore A23187, thrombin, histamine, and nitric oxide were measured.
- Correlation between vascular responses and intimal proliferative lesions was assessed.
Main Results:
- CABGs consistently showed dose- and endothelium-dependent relaxation to vasodilators.
- No significant differences in responses were found based on graft duration (7 months to 12 years).
- Marked differences in relaxant responses along the graft length correlated inversely with intimal proliferative lesions.
Conclusions:
- Long-term transplanted human saphenous vein grafts maintain endothelium-dependent responses.
- Severe intimal proliferative lesions, rather than graft duration, significantly alter graft reactivity.
- These findings highlight the importance of managing intimal hyperplasia in transplanted CABGs.
Abstract:
In the present study, responses of long-term human coronary artery bypass grafts (CABGs) to known endothelium-dependent vasodilators, acetylcholine, calcium ionophore A23187, thrombin, and histamine, as well as authentic nitric oxide, the putative endothelium-derived relaxing factor, were studied. Sixteen CAGBs were isolated within 1-2 hours from hearts of 14 patients receiving a cardiac transplant. A total of 109 ring segments were prepared from these CABGs and studied in vitro. The duration of the CABGs ranged from 7 months to 12 years. Addition of acetylcholine (0.01-10 microM), calcium ionophore A23187 (0.01-1.0 microM), thrombin (0.01-1.0 unit/ml), and histamine (0.01-1.0 microM) consistently produced a dose- and endothelium-dependent relaxation, reaching a maximum of -35.3 +/- 3.3%, -45.3 +/- 5.5%, -26.9 +/- 4.8%, and -17.8 +/- 2.5% (mean +/- SEM), respectively. No significant difference was observed among the CABGs with different duration of transplantation, whereas the relaxant responses of different segments along the entire length of a CABG were markedly different. These latter differences in the endothelium-dependent responses appear to correlate inversely with the development of intimal proliferative lesions in these CABGs. Addition of nitric oxide (0.01-10 microM) produced a potent dose- and endothelium-independent relaxation, which was also slightly depressed in CABGs with severe intimal proliferation. These results demonstrate that long-term transplanted human saphenous vein grafts retain their endothelium-dependent responses and that development of severe intimal proliferative lesions, rather than the duration of the grafts, result in marked alterations in the reactivity of these transplanted CABGs.