Negative intrathoracic pressure, such as occurs in obstructive sleep apnea (OSA), increases the transmural gradient across the aorta. This could predispose to dilation or dissection, particularly when experienced in repetitive fashion over months to years. Studies have observed an association between OSA and thoracic aortic size, both in Marfan subjects [1] and among unselected subjects referred for polysomnography [2]. In addition, one small study found severity of OSA to be greater in patients with dissection vs hypertensive controls [3]. However, it is hard to say that OSA per se contributes to aortic abnormalities because of small sample size and the presence of potential confounders in published work to date [4]. Another study used the Mueller Maneuver (forced inspiration against an occluded airway, MM) as a surrogate for OSA and found that obstructive hypopnea, but not apnea, increased thoracic aortic diameter [5]. It is difficult to explain why hypopnea, but not apnea, would affect aortic diameter. In addition, this study used 2-D echocardiography which may be compromised by off-angle imaging in a straining patient. We therefore used 3-D echocardiography to evaluate changes in aortic area during performance of a sustained MM. This allowed precise alignment of the crop plane perpendicular to the aortic wall, ensuring accurate cross-sectional imaging of the aorta. This study was approved by the Einstein Healthcare Network Institutional Review Board. Twenty-two healthymale subjects≤30 years of agewere enrolled. All subjects gave informed consent before participating. Each was coached in performance of the MMwhile lying supine. A nose clip and mouthpiece were positioned before each maneuver. The mouthpiece was connected to an electronic pressure gauge and incorporated a small air leak to prevent closure of the glottis at the time of inspiratory effort. Mouth pressure was displayed in digital format for the subjects who were instructed to build negative intrathoracic pressure gradually, using the diaphragm, so as to maximize chances of obtaining suitable echocardiographic images. The goal was to achieve and maintain an intrathoracic pressure of −40 mm Hg (−54.4 cm H2O). Imaging was performed with a Philips iE33 system (Philips Medical Systems, Andover, MA) and X5-1 transducer. The “3-D zoom” mode was used, positioning the volume of interest over the left ventricular outflow tract, aortic valve, and ascending aorta. Twenty second loops were recorded, with the MM starting 4–5 s into the recording. Each subject performed 4–5MMs. The resultant 3D datasets were then used to create 2-D slices of the aorta approximately 1 cm above the sinotubular junction. Care was taken to ensure that slices were perpendicular to the aortic wall. Aortic area was measured in diastole when the aorta is relatively motionless. Multiple measurements were made at baseline and during the maneuver, with measurements averaged for each phase. All measurements weremade by a reader blinded to the nature of the study. Paired t-test analysis was used to compare the aortic area at baseline with that during the MM. Among the 22 subjects, ten had images of suitable quality for precise measurements. Of these, 6 maintained a negative inspiratory pressure of at least −30 cm H2O, a minimum value selected to mimic conditions during a naturally occurring apnea. For the group, mean aortic area at baseline was 4.01 ± 0.53 cm rising to 4.47 ± 0.58 cm during the MM (mean difference = 0.46 ± 0.08 cm, p = 0.0017, see Fig. 1). In addition, aortic area was observed to increase to a similar degree in each subject. In this study we observed an increase in aortic area under conditions of high negative intrathoracic pressure (i.e. performance of a MM). Such negative pressure is the defining characteristic of an obstructive apnea. It imposes an afterload burden on the left ventricle and increases the pressure gradient across the aortic wall. While pressure outside the aorta falls, pressure inside remains substantially the same, likely because much of the aorta is extrathoracic. Increased transmural pressure is the likely explanation for the larger aortic area that we observed during the MM. Obstructive sleep apnea is the clinical condition most relevant to this research. Patients with OSA are exposed to recurrent episodes of high negative intrathoracic pressure, up to hundreds of times per night. It is plausible that such repeated barotrauma could predispose to or cause aortic dissection. The chief limitation of this study is its small size. Many subjects could not maintain target negative intrathoracic pressure long enough to acquire useful echocardiographic images. Among those who could, many did not have crisp enough echocardiographic images to allow precise measurements. Thus, only six subjects met all conditions to allow detailed measurement of aortic area during the MM. However,