Association of intraluminal thrombus in abdominal aortic aneurysm with local hypoxia and wall weakening

Purpose: Our previous computer models suggested that intraluminal thrombus (ILT) within an abdominal aortic aneurysm (AAA) attenuates oxygen diffusion to the AAA wall, possibly causing localized hypoxia and contributing to wa ll weakening. The purpose of this work was to investigate this possibility. Methods. In one arm of this study, patients with AAA were placed in one of two groups: (1) those with an ILT of 4-mm or greater thickness on the anter ior surface or (2) those with little (< 4 nim) or no ILT at this site. Duri ng surgical resection but before aortic cross-clamping, a needle-type polar ographic partial pressure of oxygen (Po-2) electrode was inserted into the wall of the exposed AAA, and the Po-2 was measured. The probe was advanced, and measurements were made midway through the thrombus and in the lumen. M ural and mid-ILT Po-2 measurements were normalized by the intraluminal Po-2 measurement to account for patient variability. In the second arm of this study, two AAA wall specimens were obtained from two different sites of the same aneurysm at the time of surgical resection: group I specimens had thi ck adherent ILT, and group It specimens had thinner or no adherent ILT. Non aneurysmal tissue was also obtained from the infrarenal aorta of organ dono rs. Specimens were subjected to histologic, immunohistochemical, and tensil e strength analyses to provide data on degree of inflammation (% area infla mmatory cells), neovascularization (number of capillaries per high-power fi eld), and tensile strength (peak attainable load). Additional specimens wer e subjected to We-stern blotting and immunohistochemistry for qualitative e valuation of expression of the cellular hypoxia marker oxygen-regulated pro tein. Results. The Po-2 measured within the AAA wall in group I (n = 4) and group II (n = 7) patients was 18% +/- 9% luminal value versus 60% +/- 6% (mean /- SEM; P <.01). The normalized Po-2 within the ILT of group I patients was 39% +/- 10% (P =.08 with respect to the group I wall value). Group I tissu e specimens showed greater inflammation (P <.05) compared with both group I I specimens and nonaneurysmal tissue: 2.9% +/- 0.6% area (n = 7) versus 1.7 % +/- 0.3% area (n = 7) versus 0.2% +/- 0.1% area (n = 3), respectively. We found similar differences for neovascularization (number of vessels/high-p ower field), but only group I versus control was significantly different (P <.05): 16.9 +/- 1.6 (n = 7) vs 13.0 +/- 2.3 (n = 7) vs 8.7 +/- 2.0 (n = 3) , respectively. Both Western blotting and immunohistochemistry results sugg est that oxygen-regulated protein is more abundantly expressed in group I v ersus group II specimens. Tensile strength of group I specimens was signifi cantly less (P <.05) than that for group II specimens: 138 +/- 19 N/cm(2) ( n = 7) versus 216 +/- 34 N/cm(2) (n = 7), respectively. Conclusion: Our results suggest that localized hypoxia occurs in regions of thicker ILT in AAA. This may lead to increased, localized mural neovascula rization and inflammation, as well as regional wall weakening. We conclude that ILT may play an important role in the pathology and natural history of AAA.