Does endothelial dysfunction contribute to the clinical status of patients with peripheral arterial disease?
ABSTRACT Peripheral arterial disease leads to lower extremity ischemia and limb loss, and is linked to cardiovascular events. The anatomical extent of lower extremity atherosclerosis fails to fully explain ischemic symptoms or predict the development of critical limb ischemia. Endothelial dysfunction is known to contributed to the pathogenesis and clinical expression of coronary artery disease, but the importance of endothelial dysfunction in peripheral arterial disease remains incompletely understood. Endothelial dysfunction could contribute to lower extremity ischemia by impairing blood flow responses to ischemia, collateral formation and arterial remodelling, and by promoting vasospasm, thrombosis, plaque rupture and lesion progression. There is a need for additional studies examining the contribution of endothelial dysfunction to the pathogenesis of peripheral arterial disease, and the potential role of endothelial dysfunction as a surrogate marker with utility in the management of patients.
Article: Dynamic contrast-enhanced MRI assessment of hyperemic fractional microvascular blood plasma volume in peripheral arterial disease: initial findings.[show abstract] [hide abstract]
ABSTRACT: The aim of the current study was to describe a method that assesses the hyperemic microvascular blood plasma volume of the calf musculature. The reversibly albumin binding contrast agent gadofosveset was used in dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) to assess the microvascular status in patients with peripheral arterial disease (PAD) and healthy controls. In addition, the reproducibility of this method in healthy controls was determined. Ten PAD patients with intermittent claudication and 10 healthy control subjects were included. Patients underwent contrast-enhanced MR angiography of the peripheral arteries, followed by one DCE MRI examination of the musculature of the calf. Healthy control subjects were examined twice on different days to determine normative values and the interreader and interscan reproducibility of the technique. The MRI protocol comprised dynamic imaging of contrast agent wash-in under reactive hyperemia conditions of the calf musculature. Using pharmacokinetic modeling the hyperemic fractional microvascular blood plasma volume (V(p), unit: %) of the anterior tibial, gastrocnemius and soleus muscles was calculated. V(p) was significantly lower for all muscle groups in PAD patients (4.3±1.6%, 5.0±3.3% and 6.1±3.6% for anterior tibial, gastrocnemius and soleus muscles, respectively) compared to healthy control subjects (9.1±2.0%, 8.9±1.9% and 9.3±2.1%). Differences in V(p) between muscle groups were not significant. The coefficient of variation of V(p) varied from 10-14% and 11-16% at interscan and interreader level, respectively. Using DCE MRI after contrast-enhanced MR angiography with gadofosveset enables reproducible assessment of hyperemic fractional microvascular blood plasma volume of the calf musculature. V(p) was lower in PAD patients than in healthy controls, which reflects a promising functional (hemodynamic) biomarker for the microvascular impairment of macrovascular lesions.PLoS ONE 01/2012; 7(5):e37756. · 4.09 Impact Factor