Dietary Nitrate Supplmentation in Peripheral Artery Disease and Diabetes Mellitus+Peripheral Artery Disease
Peripheral artery disease (PAD) is a form of cardiovascular disease (CVD) caused by atherosclerotic occlusions in the legs. It affects approximately 5% of the US population over 50 years of age, one third of which suffer from ischmic leg pain that occurs with walking and improves with rest. We have previously shown that supervised exercise therapy is an efficacious treatment for PAD, with improvements of 66% in claudication pain onset time and 17% in peak walking time after 3 months of supervised training. Despite these improvements, claudication pain is still the major limiting factor to the intensity and duration of work that can be performed during training for daily activities.
Diminished nitric oxide (NO) bioavailibility is an underlying feature of CVD and PAD. NO plays an important role in inflammation, thrombosis, vascular tone, blood flow, tissue perfusion, and exercise capacity. Consequently, a therapy that would effectively deliver NO to the peripheral tissues that are under-perfused due to occlusive vascular disease is an area of our interested.
Our aim is to utilize the dietary supplmentation of nitric oxide (in the form of beetroot juice) as an intervention to acutely improve oxygenation to areas of ischema AND to chronically increase vessel growth to these ischemic areas. We are currently working with two populations to investigate the potential benefits of this intervention and treatment method.
- Increased Plasma Nitrite, Tissue Oxygenation and Functional Changes in PAD (1R21 1HL 111972-01)
- Dietary Nitrate to Augment Exercise Training Benefits in DM+PAD (1 R21 HL113717-01)
Incidence of PAD in subjects with Type II Diabetes is greatly increased in comparison to non-diabetic individuals. It is thought that diabetics may be less able to up-regulate endothelial NO production during acute exercise and in response to chronic training. Therefore, increasing dietary nitrite supplementation may hold significant potential as an effective, selective NO donor for acute and chronic tissue ischemia and a means of effective therapy for individuals with both diabetes and PAD.
Through these interventions, we hope to improve exercise tolerance, overall function, and quality of life for these individuals with PAD as well as contribute valuable treatment possibilities to the medical community.
Acoustic Radiation Force Imaging of Carotid Plaque Morphology and Composition NHLBI-2RO1HL075485
In conjunction with Duke biomedical engineers Gregg Trahey (PI) and Jeremy Dahl, and vascular surgeons Jeffrey Lawson and Ban Sileshi, we are developing and testing acoustic radiation force impulse (ARFI) imaging for detection of vulnerable carotid artery plaques.
ARFI imaging is a new ultrasonic imaging method that uses short duration (.03 - 1 meters per second) acoustic radiation force to generate localized displacements in tissue. These displacements are tracked using conventional ultrasound and correlation-based speckle-tracking methods. Tissue displacement is inversely related to tissue stiffness, and the recovery of tissue to its original position is related to its viscoelastic properties.
Because arterial walls, soft tissue, atheromas, and calcifications have a wide range in stiffness, they represent excellent candidates for ARFI imaging. Furthermore, because a single transducer on a diagnostic scanner is used to both generate the radiation force and track the resulting displacements, and there are thousands of installed ultrasonic scanners in vascular laboratories that could be programmed to include ARFI, this modality could quickly and inexpensively be added to current vascular diagnostic methods. The aim of this grant is to further develop the tecnology of ARFI and to evaluate the potential of ARFI imaging for the generation of high-resolution images of carotid plaque composition and detecting vulnerable plaques.
Above is a longitudinal view of a stiff, possibly fibrous, plaque in the common carotid artery of a 49-year-old male. The B-mode image indicates a plaque on the far wall of the common carotid artery. The plaque appears to wrap around a significant portion of the artery (for cross-section scans, not shown here), and is therefore visible on the near wall of the common carotid artery. The plaque appears to be homogeneously stiff throughout.
In contrast, below is an example of an apparently heterogeneous plaque containing a soft region surrounded by a stiff cap in the carotid bifurcation of a 55-year-old female volunteer. The plaque is located near the bifurcation of the carotid artery and is visible on both the proximal and distal walls. The soft region of the plaque is visible on the distal wall as the oval shaped region extending from 23 to 25 mm depth and -2 to 4 mm laterally in the ARFI image.
The soft region is surrounded by a significantly stiffer region. The displacement of the soft region ranges from 2.5 - 4 µm, compared to 0.5 - 1 µm in the surrounding stiffer tissue. The surrounding tissue is approximately 1.3 mm thick between the soft region and the vessel lumen, except on the left side, where the thickness of the cap decreases to approximately 0.7 mm. At 0.7 mm, the stiff cap may be considered to be at the upper limit of the range indicating vulnerability (Ge et al., 1999). Ge et al. (1999) also noted that a lipid core with area greater than 1 mm2or a core-to-plaque ratio greater than 20 percent also correlated well with rupture. The soft region in this plaque meets Ge’s definition of a vulnerable plaque, assuming that this region is a lipid core.
We are also working toward development of 3-D modeling of carotid arteries and plaques to enable us to match accurately with histology samples.
Click here for further information about our previous research studies.