Thromboxane A2: an endothelium-derived vasoconstrictor in human internal mammary arteries.

The internal mammary artery (IMA) has become the conduct of choice for coronary artery bypass grafting. However, the IMA graft can exhibit vasoconstriction during the perioperative period. Experiments were designed to determine the role of cyclooxygenase products in human IMA during hypoxia. Rings of IMA, with and without endothelium, were suspended in organ baths containing physiologic salt solution. Rings were contracted with norepinephrine and then exposed to hypoxia for 15 minutes. In segments with endothelium, hypoxia induced a transient relaxation followed by contraction. This contraction was associated with a significantly increased production of thromboxane B2, the stable metabolite of thromboxane A2 (n = 10; from 120.7 +/- 3.5 pg/mg wet tissue before hypoxia to 175.8 +/- 5.2 pg/mg during hypoxia; p < 0.05). This hypoxic contraction could be attenuated by indomethacin. However, thromboxane B2 could not be detected in samples from organ baths containing IMA segments without endothelium before or during hypoxia. This study demonstrated that endothelium of human IMA grafts releases thromboxane A2 basally and that production is augmented by hypoxia, which acts to constrict the underlying vascular smooth muscle, increase vascular tone, and promote ischemic events such as vasospasm and thrombosis, particularly in hypoxemic patients.