Association of artery wall hypoxia and cellular proliferation at a vascular anastomosis

We hypothesize that arterial wall hypoxia incites the pathologic formation of intimal hyperplasia at an artery anastomosis. We have determined from previous studies performed in our laboratory, the oxygen tension profiles of the artery wall at various times after vascular anastomosis. The purpose of this study is to determine the rate of cellular proliferation at an artery anastomosis when the artery wall is most hypoxic.

Expanded polytetrafluoroethylene (ePTFE) grafts were placed end to end in the infrarenal aorta of 27 New Zealand white rabbits. The anastomotic aortic wall oxygen (O(2)) tensions were measured with an O(2) microelectrode in rabbits 0, 7, 14, 28, and 42 days after surgery. O(2) tensions were also measured in 4 control rabbits for comparison. 5-Bromo-2'-deoxyuridine (BrDU) was injected intraperitoneally 24 h prior to rabbit sacrifice. After O(2) tension measurements, the rabbits were sacrificed and the aortic grafts were harvested. Bioquant morphometrics was used to measure cells with BrDU counterstaining and intimal thickness in 17 rabbits: in control (n = 4), Day 0 (n = 4), 7 (n = 5), and 42 (n = 4). Student's t test was used to compare O(2) tensions, cellular proliferation, and intimal hyperplasia between days.

The pO(2) levels at the outer layers of the aorta, 1 mm distal to the distal aortic graft anastomosis, were 61.0 +/- 2 (+/-SE) mm Hg for controls, 19.8 +/- 1 mm Hg for Day 7 (P < 0.0001), 19.0 +/- 1 mm Hg for Day 14, 39.2 +/- 1 mm Hg for Day 28, and 58.5 +/- 1 mm Hg for Day 42 aortic grafts. BrDU-staining ratios in the intima were significantly higher in the Day 7 aortic grafts, 28.6 +/- 3%, versus BrDU-staining ratio, 1.4 +/- 1%, in Day 42 aortic grafts (P < 0.0002).

Cellular proliferation is highest at Day 7 when the artery wall is most hypoxic and returns to baseline as O(2) tensions normalize.