Abstract P449: A Murine Model of Mid-Thoracic Aortic Coarctation

Abstract

Vascular pressure can directly affect cardiovascular structure and function. Understanding the mechanisms, however, is complicated because conditions or interventions that chronically raise blood pressure (e.g. excess angiotensin II) can also have direct effects on the vasculature that occur independent of changes in blood pressure. One approach to mitigating this problem is to obstruct flow in a vascular segment sufficiently to reduce blood pressure in the segment downstream of the obstruction, while pressure upstream either stays the same or increases. As a result, all factors other than pressure are expected to be the same in upstream and downstream vascular segments. We have found evidence that differences in intravascular pressure can also affect closely adjacent tissues, specifically perivascular adipose tissue (PVAT). To test this idea in vivo , we developed a method to produce chronic, partial occlusion (or coarctation) of the mid-thoracic aorta in mice. This exposes upstream aortic PVAT depots to significantly higher aortic pressure than downstream aortic PVAT depots. The key to the method is producing a stable occlusion with a diameter small enough to produce a pressure gradient but not so small that the downstream flow is inadequate to support tissue oxygenation. To this end, a thoracotomy was performed to expose the thoracic aorta in adult mice anesthetized with isoflurane and artificially ventilated. A coarctation of the mid-thoracic aorta was produced by tying a ligature around the aorta and a blunted needle on the aorta, then removing the needle. In other mice, a silicone rubber or nitrile O-ring of varying dimensions was placed around the aorta. Mice were allowed to recover for varying periods of time (weeks), then the degree of coarctation was evaluated using both imaging methods (ultrasound) and direct measurement of the pressure gradient (catheters placed in a carotid and a femoral artery) under isoflurane anesthesia. In a group of 9 male mice with coarctation and 4 male mice with sham coarctation, we found an average mean arterial pressure gradient of 11.7 ± 5.0 mmHg (mean ± SEM) in coarct mice and 1.6 ± 2.0 mmHg in sham mice. Systolic pressure gradients averaged 14.0 ± 5.9 mmHg in coarct mice and 1.0 ± 3.2 mmHg in sham mice. These results suggest it is possible to produce a stable pressure gradient across the thoracic aorta of mice as a tool to explore the impact of arterial pressure on vascular and PVAT structure and function.