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It was the goal of this study to compare endothelium-dependent and endothelium-independent flow reserve in vascular regions supplied by the left internal mammary artery before and after bypass graft surgery.The native internal mammary artery in situ was investigated in 13 patients (age 61.8±8.0 years) with angiographically proven coronary artery disease. The internal mammary artery after bypass grafting was investigated in ten patients (age 60.8±7.3 years) 3.5±2.8 years after the operation. Flow reserve was evaluated endothelium-dependent with acetylcholine (ACh 25 and 50 μg i.c.) and endothelium-independent with nitroglycerin (NTG 0.3 mg i.c.) followed by papaverin (10 mg i.c.). Flow indices were calculated from intraluminal Doppler blood flow velocity measurements and the vascular cross-sectional area as determined by quantitative angiography. An index for vascular resistance was defined as the ratio of pressure gradient and resting or peak flow.After endothelium-dependent stimulation with acetylcholine 25 μg (50 μg), flow in the internal mammary increased by 352.3±152% (412±145%) before surgery, whereas it increased only by 213±134% (193±120%) after surgery (P<0.05). Endothelium independent stimulation with papaverin resulted in a flow increase of 391±234% before surgery vs. 315±135% after surgery (n.s.). The resistance index decreased after endothelium-dependent stimulation with acetylcholine 25 μg (50 μg) to 35±16.8% (28±8.9%) before surgery, whereas it decreased only to 59±26% (72±43%) after surgery (P<0.05). Endothelium independent stimulation with papaverin resulted in a decrease of the vascular resistance index to 31±14% before surgery vs. 32±14% after surgery (n.s.).Vascular regions supplied by the internal mammary artery as a graft demonstrate a significantly reduced endothelium-dependent flow reserve but a preserved endothelium-independent flow reserve as compared to vascular regions supplied by the native internal mammary artery. The selective decrease in endothelium-dependent flow reserve may be due to microvascular changes in the myocardial region supplied by the internal mammary artery after bypass grafting.