Screening aortic drug treatments through arterial compliance measurements.
Abdominal aortic aneurysm (AAA) is a common and deadly problem. The aortic diameter increases in association with a complex remodeling process that includes changes in the structure and content of key proteins, elastin and collagen. As these changes occur, the tissue mechanical properties also change. The natural history of AAA is progressive enlargement to a point of mechanical tissue failure typically followed by death. Currently, the marker used to predict the risk of impending rupture is the largest transverse diameter. After reaching a diameter threshold of 5.5 cm the AAA needs to be surgically repaired. This criterion does not consider any patient-specific information or heterogeneity of the AAA that may, in some cases, lead to rupture before the AAA reaches the standard intervention threshold. Conversely, in many patients, continued observation beyond this threshold is safe. While no medical treatment is yet approved, doxycycline (Doxy) has been shown to greatly reduce AAA growth in animal models and has been shown to slow growth in 1 small clinical trial. While larger prospective randomized trials are needed, one unknown is what effect Doxy has on the structural integrity of the aortic wall. That is, does slowed AAA growth, by Doxy treatment, prevent rupture, or does the wall continue to weaken and the AAA instead ruptures at a smaller diameter? Using an established animal model of AAA, we begun to determine the changes in tissue mechanics compliance of the aorta as the AAA develops. Our current research is focused on verifying that these changes mimic the observed changes seen in the human population as reported by other researchers, so that we can confidently study how potential drug therapies may affect wall strength and compliance in the human population. The long-term objectives are to understand better factors related to progression of AAA and help verify that drug therapy with Doxy will decrease the chance of rupture by preventing wall weakening and maintaining function of the aorta.
Rentschler
Mark E
ME
Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA. markrentschler@gmail.com
Baxter
B Timothy
BT
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D001019:Aortic Rupture / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D035843:Biomedical Research; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D003187:Compliance; D018450:Disease Progression; D004318:Doxycycline / Q000627:therapeutic use; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D051379:Mice; D023421:Models, Animal; D008955:Models, Cardiovascular; D018579:Patient Selection; D016896:Treatment Outcome; D014656:Vascular Surgical Procedures
D002317:Cardiovascular Agents; D004318:Doxycycline