The relationship between geometry and hemodynamics of the stenotic carotid artery based on computational fluid dynamics.

OBJECTIVE: The purpose of this work was to investigate the relationship between the geometric factors and the hemodynamics of the stenotic carotid artery. METHODS: We retrospectively reviewed data of patients with carotid stenosis (40%-95%). The Navier-Stokes equations were solved using ANSYS CFX 18.0. Correlation analysis was based on Spearman's test. Geometric variables (p < 0.1 in the univariate analysis) were entered into the logistical regression. A receiver-operating characteristics analysis was used to detect hemodynamically significant lesions. RESULTS: 81 patients (96 arteries) were evaluated. The logistic regression analysis revealed that the translesional pressure ratio was significantly correlated with the stenosis degree (OR = 1.147, p < 0.001) and the angle between internal carotid artery and external carotid artery (angle γ) (OR = 0.933, p = 0.01). The translesional wall shear stress ratio was significantly correlated with stenosis degree (OR = 1.094, p < 0.001), lesion length (OR = 0.873, p = 0.01), lumen area of internal carotid artery (OR = 0.867, p = 0.002), and lumen area of common carotid artery (OR = 1.058, p = 0.01). For predicting low translesional pressure ratio, the AUC was 0.71 (p < 0.001) for angle γ, and was 0.87 (p < 0.001) for stenosis degree. For predicting high translesional wall shear stress ratio, the AUC was 0.62 (p = 0.04) for lumen area of internal carotid artery, and was 0.77 (p < 0.001) for stenosis degree. CONCLUSIONS: Apart from stenosis degree, other geometric characteristics of lesions may also have an influence on hemodynamics of the stenotic carotid artery.

The pathogenesis of aging-induced left atrial appendage thrombus formation and cardioembolic stroke in mice is influenced by inflammation-derived matrix metalloproteinases.

Elderly people without atrial fibrillation (AF) still have a high incidence of cardioembolic stroke, suggesting that thrombus formation within the left atrial appendage (LAA) may also occur in an AF-independent manner. In the present study, we explored the potential mechanisms for aging-induced LAA thrombus formation and stroke in mice. We monitored stroke events in 180 aging male mice (14-24 months) and assessed left atrium (LA) remodeling by echocardiography at different ages. Mice that had stroke were implanted with telemeters to confirm AF. Histological features of LA and LAA thrombi were examined, as well as collagen content, expression of matrix metalloproteinases (MMPs), and leukocyte density in the atria at different ages, in mice with or without stroke. Also, the effects of MMP inhibition on stroke incidence and atrial inflammation were tested. We detected 20 mice (11 %) with stroke, 60 % of which were within 18-19 months of age. Although we did not detect AF in mice with stroke, we detected the presence of LAA thrombi, suggesting that stroke originated from the hearts of these mice. Compared with 18-month-old mice without stroke, 18-month-old stroke mice had enlarged LA with a very thin endocardium, that was associated with less collagen and heightened MMP expression in the atria. During aging, we found that the expression of mRNAs for atrial MMP7, MMP8, and MMP9 peaked at 18 months, which closely correlated with reductions in collagen content and the time-window for cardioembolic stroke in these mice. Treatment of mice with an MMP inhibitor at 17-18 months of age reduced atrial inflammation and remodeling, and stroke incidence. Taken together, our study demonstrates that aging-induced LAA thrombus formation occurs through a mechanism involving upregulation of MMPs and breakdown of collagen, and that treatment with an MMP inhibitor may be effective as a treatment strategy for this heart condition.

Quantitative Assessment of Changes in Hemodynamics After Obliteration of Large Intracranial Carotid Aneurysms Using Computational Fluid Dynamics.

Background: It was speculated that the alteration of the geometry of the artery might lead to hemodynamic changes of distal arteries. This study was to investigate the hemodynamic changes of distal arterial trees, and to identify the factors accounting for hyperperfusion after the obliteration of large intracranial aneurysms. Methods: We retrospectively reviewed data of 12 patients with intracranial carotid aneurysms. Parametric models with intracranial carotid aneurysm were created. Patient-specific geometries were generated by three-dimensional rotational angiography. To mimic the arterial geometries after complete obliteration of the aneurysms, the aneurysms were virtually removed. The Navier-Stokes equations were solved using ANSYS CFX 14. The average wall shear stress, pressure and flow velocity were measured. Results: Pressure ratio values were significantly higher in A1 segments, M1 segments, and M2 + M3 segments after obliteration of the aneurysms (p = 0.048 in A1 segments, p = 0.017 in M1 segments, p = 0.001 in M2 + M3 segments). Velocity ratio values were significantly higher in M1 segments and M2 + M3 segments after obliteration of the aneurysms (p = 0.047 in M1 segments, p = 0.046 in M2 + M3 segments). The percentage of pressure ratio increase after obliteration of aneurysms was significantly correlated with aneurysmal angle (r = 0.739, p = 0.006 for M2 + M3). Conclusions: The pressure and flow velocity of distal arterial trees became higher after obliteration of aneurysms. The angle between the aneurysm and the parent artery was the factor accounting for pressure increase after treatment.

Inhibition of Platelets by Clopidogrel Suppressed Ang II-Induced Vascular Inflammation, Oxidative Stress, and Remodeling.

Background Platelets play a role in promoting inflammatory responses under several disease conditions. Platelets are activated in hypertensive patients. However, the mechanisms responsible for platelet-mediating vascular inflammation are unknown. The present study investigated the role of platelets in promoting vascular inflammation following angiotensin II (Ang II ) stimulation, and the efficacy of antiplatelet intervention. Methods and Results Within a mouse model of Ang II infusion (490 ng/kg per min), we measured the portion of P-selectin-positive platelets and platelet-monocyte (P-M) binding in blood samples, and platelet accumulation and P-M binding in vessels under Ang II stimulation at days 1, 3, and 7. We tested the efficacy of clopidogrel (15 mg/kg per day, followed by 5 mg/kg per day) on Ang II -induced platelet activation, P-M binding, vascular platelet accumulation, as well as vascular inflammation and remodeling at day 7 or 14. Clopidogrel reduced platelet vascular deposition (28.7±2.4% versus 18.3±2.9%), suppressed inflammatory cell infiltration (3.6±0.8×104/vessel versus 2.3±1.2×104/vessel) and oxidative stress, and attenuated vascular remodeling and dysfunction (55.0±5.5% versus 84.0±6.0%) following Ang II stimulation at day 7 or 14. Clopidogrel suppressed Ang II -induced P-M binding both at circulating (13.4±3.3% versus 5.9±2.7%) and regional (33.4±4.3% versus 11.9±2.7%) levels. Conclusions Platelets play a critical role in vascular inflammation under Ang II stimulation, with a marked promotion of P-M binding as an important mechanism. Clopidogrel prevented vascular inflammation in Ang II -infused mice.