Lack of ecto-5'-nucleotidase (CD73) promotes arteriogenesis.

AIMS: Adenosine can stimulate angiogenesis, but its role in the distinct process of arteriogenesis is unknown. We have previously reported that mice lacking ecto-5'-nucleotidase (CD73-/-) show enhanced monocyte adhesion to the endothelium after ischaemia, which is considered to be an important trigger for arteriogenesis. METHODS AND RESULTS: Hindlimb ischaemia was induced in wild-type (WT) and CD73-/- mice to study the role of extracellularly formed adenosine in arteriogenesis. Magnetic resonance angiography (MRA) was performed for serial visualization of newly developed vessels at a spatial resolution of 1 nL, and high-energy phosphates (HEP) were quantified by (31)P MR spectroscopy (MRS). MRA of CD73-/- mice revealed substantially enhanced collateral artery conductance at day 7 [CD73-/-: 0.73 ± 0.11 a.u. (arbitrary units); WT: 0.44 ± 0.13 a.u.; P < 0.01, n = 6], and MRS of the affected hindlimb showed a faster restoration of HEP in correlation with enhanced functional recovery in the mutant. Additionally, histology showed no differences in capillary density between the groups but showed an increased monocyte infiltration in hindlimbs of CD73-/- mice. CONCLUSION: Serial assessment of dynamic changes of vessel growth and metabolism in the process of arteriogenesis demonstrate that the lack of CD73-derived adenosine importantly promotes arteriogenesis but does not alter angiogenesis in our model of hindlimb ischaemia.

Feasibility, safety, and efficacy of real-time three-dimensional transoesophageal echocardiography for guiding device closure of interatrial communications: initial clinical experience and impact on radiation exposure.

AIMS: Our aim was to assess the feasibility and safety of real-time (RT) three-dimensional (3D) transoesophageal echocardiography (TEE) for guiding transcatheter closure of interatrial communications and to evaluate its additional benefit over conventional 2D TEE in reducing radiation exposure for the patient. METHODS AND RESULTS: Twenty-five patients undergoing device closure of their interatrial defect had the procedure guided by fluoroscopy, 2D TEE, and RT 3D TEE. We retrospectively compared this group with a historical control group in which interventional guidance was performed using fluoroscopy and 2D TEE alone. The application of RT 3D TEE allowed safe device deployment in all patients without any complications, resulting in a reduction of mean fluoroscopy time (10 +/- 6 to 6 +/- 4 min, P < 0.01), mean dose area product (DAP) (964 +/- 628 to 535 +/- 464 cGy cm(2), P < 0.01), and mean DAP per individual body surface area (494 +/- 317 to 273 +/- 221 cGy cm(2)/m(2), P < 0.01). CONCLUSION: RT 3D TEE as an adjunct to 2D TEE is a feasible and safe tool to guide transcatheter device closure of interatrial communications, resulting in a reduction of radiation exposure. These data indicate that RT 3D TEE can be used to safely monitor interatrial defect closure in clinical routine.

Dynamic changes in murine vessel geometry assessed by high-resolution magnetic resonance angiography: a 9.4T study.

PURPOSE: To establish high-resolution magnetic resonance angiography (MRA) protocols to monitor and quantify dynamic changes of vascular remodeling in pathologic mouse models. MATERIALS AND METHODS: Time-of-flight (TOF) MRA of murine vessels was performed at 9.4T to monitor temporal alterations in the vessel structure in two frequently used injury models (wire denudation of carotid artery and femoral artery occlusion). Quantification of vessel morphology was performed with the use of in-house-developed software and validated by estimation of inter- and intraobserver variabilities and reproducibility, and by correlation with histological data. RESULTS: MRA-based volume determination exhibited low intra- and interobserver variabilities and high reproducibility. Furthermore, good correlations with histological data were found four weeks after injury (R2=0.970). Two high-resolution image series are presented to demonstrate the applicability of the technique: 1) the time course of a vessel stenosis that reopens by thrombus recanalization, and 2) the continuous restoration of blood flow by collateral vessel formation during arteriogenesis after induction of hindlimb ischemia. CONCLUSION: We describe high-resolution MRA imaging protocols that are suitable for sensitively measuring the extent and time course of changes in vessel morphology in mice in a repetitive manner without any contrast agent. This methodology provides a reliable tool for noninvasive monitoring of vascular lesion development or neovascularization in transgenic mice.