Three Dimensional Quantification of Angiotensin II-Induced Murine Abdominal Aortic Aneurysms Using High Frequency Ultrasound

Abdominal aortic aneurysms (AAAs), a localized dilation of the vessel wall of 50% or more above normal, claims approximately 14,000 U.S. lives yearly due to aortic rupture. This commonly asymptomatic disease can only be treated by endovascular stent grafts or invasive surgery, usually after the AAA diameter reaches 5 cm. Because these treatment methods carry serious risk, stem cell therapy is being explored in order to provide a low risk option for managing smaller AAAs. To determine if stem cell therapy, once administered, could stabilize or reduce AAA growth, baseline 3D ultrasound measurements in a control group were first needed. High frequency ultrasound was used on apolipoprotein E-deficient (apoE-/-) mice given angiotensin II (AngII) from subcutaneously implanted osmotic mini pumps. This mouse model developed dissecting AAAs, containing a false and true lumen, which were clearly visualized and quantified using 3D ultrasound imaging. With this ultrasound technique, we found that aneurysm diameter, total volume, and false lumen volume all increased steadily over a period of 28 days once AAAs formed. These data suggest our noninvasive, 3D ultrasound technique can be used to monitor the progression of aneurysms that may be delayed once stem cell therapy is administered

The impact of maternal exercise during pregnancy on cardiovascular health in rodent and swine offspring

Atherosclerotic cardiovascular disease (CVD) is currently the leading cause of death in the U.S. Research has indicated that maternal behaviors during pregnancy can influence an offspring\u27s susceptibility to CVD later in life. The majority of literature to date has examined the impact of negative maternal behaviors during pregnancy on offspring disease risk, while very few have examined positive maternal behaviors. Therefore, the purpose of this thesis was to test the hypothesis that maternal exercise during pregnancy improves endothelial function in standard-chow fed rodent and high-fat fed swine offspring at 4 and 8 months of age. The rodent study utilized pregnant female Sprague Dawley rats that were divided into sedentary (n = 10) or exercise (n =9) groups. The exercise group had voluntary access to a running wheel throughout pregnancy. Pregnant sows were used for the swine study. The sows were divided into exercise-trained (n = 8) and sedentary (n = 8) groups. The exercise-trained group ran on a treadmill 5 days/week for 25-40 minutes at 2.5 mph throughout pregnancy. At 4 or 8 months, the abdominal aorta was harvested from rodent offspring, while the femoral and left anterior descending (LAD) artery was harvested from swine offspring. Cumulative doses of endothelium-dependent (rodent: acetylcholine/10 -10-10-4M; swine: bradykinin/10-10-10 -6M) and independent (rodent and swine: sodium nitroprusside/10 -10-10-4M) vasodilators were utilized for in vitro vascular function experiments using the respective arteries for each animal model. A portion of the femoral and LAD arteries for the swine offspring were also stored in neutral buffered formalin, trimmed of connective tissue, and stained with haematoxyloin and eosin for histological purposes. For both the rodent and swine offspring there were no significant differences between the exercise and sedentary offspring\u27s vascular function responses to endothelium-dependent or –independent vasodilators at 4 or 8 months of age. Additionally, there were no significant differences in atherosclerotic lesion formation between exercise and sedentary high-fat fed swine offspring. In conclusion, maternal exercise does not significantly alter vascular function in adult standard-chow fed rodent and high-fat fed swine offspring at 4 and 8 months of age