Endothelium-dependent production of prostacyclin in human internal mammary artery.
The internal mammary artery (IMA) has become the conduit of choice in coronary artery bypass surgery because of superior long-term patency. It had been shown that IMA graft could release prostacyclin. Prostacyclin is a potent vasodilator and also can inhibit platelet aggregation. To determine the role of human IMA endothelium in production of prostacyclin, we tested the reactivity of segments of human IMA to hypoxia in vitro. Human IMAs were harvested during coronary artery bypass surgery. Prostacyclin was measured from fluid in the organ baths by radioimmunoassay of its major hydrolytic product 6-keto-prostaglandin F1 alpha. Rings (4 mm in length) of IMA, with and without endothelium, were suspended in organ baths containing physiologic salt solution. Rings were contracted with norepinephrine, and exposed to hypoxia (pO2 35 +/- 5 mmHg) for 15 minutes then reoxygenated. In segments with endothelium, hypoxia induced a transient relaxation followed by contraction. The transient relaxation was associated with a significantly increased production of 6-keto-prostaglandin-F1 alpha (from 34.1 +/- 2.7 pg/ml prehypoxia to 51.6 +/- 6.7 pg/ml during hypoxia, mean +/- SEM, p less than 0.05). This transient relaxation was blocked by indomethacin but not by NG-monomethyl-L-arginine (L-NMMA) and free radical scavengers (superoxide dismutase, catalase and deferoxamine). However, in segments without endothelium, the prehypoxia (14.7 +/- 0.9) and during hypoxia (15.5 +/- 1.4) level of 6-keto-prostaglandin F1 alpha were not increased and were significantly lower than those with endothelium. This study demonstrated that endothelium of IMA grafts could release prostacyclin either in a basal condition or upon stimulation of hypoxia. This ability possibly contributes to its long-term patency.
Lin
P J
PJ
Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan, R.O.C.
Chang
C H
CH
Chu
J J
JJ
Chang
J P
JP
Liu
H P
HP
Hsieh
H C
HC
Hsieh
M C
MC
D015687:Cell Hypoxia; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D008323:Mammary Arteries / Q000378:metabolism*
D011464:Epoprostenol