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 wall 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 anterior surface or (2) those with little (< 4 mm) or no ILT at this site. During surgical resection but before aortic cross-clamping, a needle-type polarographic partial pressure of oxygen (PO2) electrode was inserted into the wall of the exposed AAA, and the PO2 was measured. The probe was advanced, and measurements were made midway through the thrombus and in the lumen. Mural and mid-ILT PO2 measurements were normalized by the intraluminal PO2 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 thick adherent ILT, and group II specimens had thinner or no adherent ILT. Nonaneurysmal tissue was also obtained from the infrarenal aorta of organ donors. Specimens were subjected to histologic, immunohistochemical, and tensile strength analyses to provide data on degree of inflammation (% area inflammatory cells), neovascularization (number of capillaries per high-power field), and tensile strength (peak attainable load). Additional specimens were subjected to Western blotting and immunohistochemistry for qualitative evaluation of expression of the cellular hypoxia marker oxygen-regulated protein.
Results: The PO2 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 PO2 within the ILT of group I patients was 39% +/- 10% (P =.08 with respect to the group I wall value). Group I tissue specimens showed greater inflammation (P <.05) compared with both group II 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-power 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 suggest that oxygen-regulated protein is more abundantly expressed in group I versus group II specimens. Tensile strength of group I specimens was significantly less (P <.05) than that for group II specimens: 138 +/- 19 N/cm2 (n = 7) versus 216 +/- 34 N/cm2 (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 neovascularization 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.