| Objectives: The long-term benefit of myocardial revascularization depends largely on the long-term patency of bypass grafts. It is widely accepted that the long-term patency of internal mammary artery (IMA) graft is superior to that of saphenous vein (SV) graft. However, the main causes contributing to the different patency rate between arterial and venous coronary bypass grafts such as IMA, radial artery (RA) and SV still remain unknown.It has been demonstrated that vascular endothelium plays a key role in the regulation of vascular tone and homeostasis. Apparently, endothelial function of the coronary bypass grafts is crucial to the long-term graft patency. In response to a variety of stimuli, endothelial cells generate three major endothelium-derived relaxing factors (EDRFs)-nitric oxide (NO), prostacyclin (PGI2) and endothelium-derived hyperpolarizing factor (EDHF). Among those, NO and PGI2 have attracted a major attention. A great amount of information concerning the physiological effects and biosynthesis of NO and PGI2 has been acquired. Experimental studies have demonstrated that IMA has greater basal and stimulated production of PGI2 than SV and that the endothelium-dependent relaxation is significantly greater in IMA than in SV. However, direct measurement of NO released from IMA, RA and SV has never been performed. Moreover, the role of the third component of EDRFs, i.e. EDHF, in human coronary bypass grafts has not been well studied either.The present study was designed to examine (1) the differences of NO release and EDHF-mediated hyperpolarizaiton of the smooth muscle cells (SMC) of IMA, RA and SV (2) the chemical nature and the diffusibility of EDHF released from IMA and SV (3) the impact of surgical preparation of SV on NO release.Material and Methods: Human IMA, RA, and SV segments taken from patients undergoing coronary artery bypass grafting were placed in a 3ml organ chamber, which is supperfused with Crebs solution at a constant rate of 3ml/min and kept at 37℃. NO-sensitive electrode connected to NO meter was used to directly measure the NO release from the endothelium. Conventional intracellular glass microelectrode was used to directly measure the membrane potential changes of the SMC of IMA, RA and SV in response to acetylcholine (ACh) and bradykinin (BK) before and after incubation with NG-nitro-L-arginine (L-NNA, 300μM, a NO synthase inhibitor), indomethacin (Indo, 7μM, a cyclooxygenase inhibitor) and oxyhemoglobin (OHb, 20μM, a NO scavenger). To evaluate the role of cytochrome P-450 monooxygenase on the EDHF-mediated hyperpolarizaiton of SMC of IMA and SV, 17-ODYA (10 μM) and miconazol (5 μM), the cytochrome P-450 monooxygenase inhibitors, were used to block the cytochrome P-450 pathway. In a separate experiment, direct measurement of NO release from the surgically prepared SVs compared with the control veins was performed.Results: (1) The basal release of NO in the IMA is 16.8 ±1.6 nM (n=8), significantly greater than that in RA (11.1 ± 1.0 nM, n=6, p<0.05) and SV (9.9 ± 2.8nM, n=9, p<0.01). Compared with SV, the basal release of NO in RA is increased (p<0.05). (2) The concentration of ACh or BK stimulated release of NO in the IMA is significantly higher than that in RA and SV, while there was no significant difference between RA and SV. (3) Both basal and stimulated release of NO in the surgically prepared SVs are significantly decreased compared with the control veins. (4) The EDHF-mediated hyperpolarization of SMC are more significant in the IMA compared with RA and SV (for ACh -5 log M: 9.4 ± 1.5 mV, n=10 vs. 4.5 ± 1.1 mV, n=17, p<0.01, IMA vs. SV; for BK-7 log M: 10.9 ± 1.5 mV, n=8, vs. 5.1 ± 0.5 mV, n=8, p<0.01, IMA vs. SV; 10.9 ± 1.5 mV, n=8, vs. 5.8 ± 0.9 mV, n=6, p<0.05, IMA vs. RA). There was no significant difference of EDHF-mediated hyperpolarization of SMC between RA and SV. (5) Addition of 17-ODYA and miconazol did not significantly change the EDHF-mediated hyperpolarization of the SMC...
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