Detection of Hypoxia in Human Thoracic Aorta Using Pimonidazole-HCl

Marie Billaud, PhD
Department of Surgery
Division of Cardiac Surgery
Poster Overview

Aortic aneurysm is an abnormal bulge of the aorta, the largest artery in the body, and affect approximately 15,000 people in the United States each year. The only treatment available is open-heart surgery to remove the aneurysmal aorta if its size exceeds 55mm (approximately twice the size of a normal aorta). However, life-threatening complications occur in patients with aortic size below this threshold. Our goal is to develop new diagnostic tools to help surgeons identify aneurysmal patients at risk of complications. To this end, we developed a clinical trial aimed at detecting areas of low oxygen in the aortic wall, since our previous work suggested that low oxygen (hypoxia) may be involved in the disease process of aortic  aneurysms. A few hours before surgery, patients enrolled in this trial took a drug that is incorporated by hypoxic cells. During the operation, the surgeon removed the aorta and the drug was detected in the lab. We found the drug mainly in aneurysmal area with severe tissue damage. We hope to use these findings to develop new diagnostic methods whereby areas of hypoxia are detected via routine clinical imagine such as CT scans to identify patients at risk for aortic complications.

Scientific Abstract

Ascending aortic aneurysm represents a serious clinical problem portending a risk of aortic dissection. Current surgical guidelines are primarily based on aortic size and recommend surgical intervention when the aortic diameter reaches 55mm. However, ~50% of dissection occurs in patients with aortic diameter well below this threshold highlighting a critical need for better diagnostic tools and a better understanding of the disease. Our previous work suggested that hypoxic areas may be found in the aneurysmal aortic wall likely as a cause, though possibly a consequence of the associated adventitial vasa vasorum remodeling. We thus developed a study aimed at detecting hypoxia in human ascending aortas using pimonidazole-HCL, a drug incorporated by hypoxic cells. Patients with ascending aortic aneurysms self-administered the study drug per os 4-6h before surgical aortic replacement. Detection of the drug in aortic specimens via immunolabelling revealed that aneurysmal areas with intense tissue damage overlapped with hypoxic areas. Conversely, pimonidazole-HCL was not detected in non-aneurysmal areas. This clinical trial provides the basis for future studies aimed at detecting tissue hypoxia non-invasively using 18F-FMISO, a pimonidazole-derived compound detectable via PET-CT.

Clinical Implications
This clinical trial was designed to detect areas of low oxygen in aortic aneurysms with the goal to use low oxygen as a marker of aortic damage severity and identify patients at risk of aortic complications.
Research Areas
Authors
Marie Billaud, Tara D. Richards, Jennifer C. Hill, Julie A. Phillippi, Thomas. G. Gleason
Principal Investigator
Thomas Gleason

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