Extracranial carotid artery aneurysms (ECAAs) are rare, and the optimal therapeutic modality for these lesions remains controversial. Surgical resection and covered stents may be limited to selected cases. While the concept of using flow diversion is appealing for large aneurysms, the application of flow diverters in extracranial carotid lesions may face restrictions due to off-label use, reimbursement challenges, and factors related to the devices themselves. We report our experience with multiple overlapping Low-profile Visualized Intraluminal Support (LVIS) stents as a reconstructive option for selected ECAAs. Five patients with large ECAAs were treated with multiple overlapping LVIS stents. The primary goal was parent-artery reconstruction and reduction of intra-aneurysmal flow reduction by increasing local metal coverage across the neck of the aneurysm. Double overlapping LVIS stents were used in 3 cases, whereas triple or more extensive overlapping constructs were used in 2 cases. During a mean radiologic follow-up of 24 months, complete occlusion in 2 cases, partial occlusion in 3 cases, and adjunctive procedures in 3 cases were required, and no major thromboembolic or hemorrhagic complications were documented. Adjunctive or staged treatment was required in 3 cases, including balloon angioplasty, additional LVIS stenting, flow-diverter placement, stent-graft placement, or coil embolization. Multiple overlapping LVIS stenting is a feasible and relatively safe reconstructive option for selected large or clinically significant ECAAs, particularly when primary flow-diverter treatment is constrained by off-label indication or reimbursement issues. However, they have limited standalone efficacy, particularly in large or complex aneurysms, often requiring adjunctive or staged treatment.

Cells can resist and even recover from stress induced by acute hypoxia, whereas chronic hypoxia often leads to irreversible damage and eventually death. Although little is known about the response(s) to acute hypoxia in neuronal cells, alterations in ion channel activity could be preferential. This study aimed to elucidate which channel type is involved in the response to acute hypoxia in rat pheochromocytomal (PC12) cells as a neuronal cell model. Using perfusing solution saturated with 95% N2 and 5% CO2, induction of cell hypoxia was confirmed based on increased intracellular Ca2+ with diminished oxygen content in the perfusate. During acute hypoxia, one channel type with a conductance of about 30 pS (2.5 pA at -80 mV) was activated within the first 2~3 min following onset of hypoxia and was long-lived for more than 300 ms with high open probability (Po, up to 0.8). This channel was permeable to Na+ ions, but not to K+, Ca+, and Cl- ions, and was sensitively blocked by amiloride (200 nM). These characteristics and behaviors were quite similar to those of epithelial sodium channel (ENaC). RT-PCR and Western blot analyses confirmed that ENaC channel was endogenously expressed in PC12 cells. Taken together, a 30-pS ENaC-like channel was activated in response to acute hypoxia in PC12 cells. This is the first evidence of an acute hypoxia-activated Na+ channel that can contribute to depolarization of the cell.
Amiloride ; Animals ; Anoxia ; Blotting, Western ; Cell Hypoxia ; Epithelial Sodium Channels ; Ion Channels ; Ions ; Neurons ; Oxygen ; PC12 Cells ; Pheochromocytoma ; Rats

A non-steroidal anti-inflammatory drug (NSAID) has many adverse effects including cardiovascular (CV) risk. Diclofenac among the nonselective NSAIDs has the highest CV risk such as congestive heart failure, which resulted commonly from the impaired cardiac pumping due to a disrupted excitation-contraction (E-C) coupling. We investigated the effects of diclofenac on the L-type calcium channels which are essential to the E-C coupling at the level of single ventricular myocytes isolated from neonatal rat heart, using the whole-cell voltage-clamp technique. Only diclofenac of three NSAIDs, including naproxen and ibuprofen, significantly reduced inward whole cell currents. At concentrations higher than 3 micrometer, diclofenac inhibited reversibly the Na+ current and did irreversibly the L-type Ca2+ channels-mediated inward current (IC50=12.89+/-0.43 micrometer) in a dose-dependent manner. However, nifedipine, a well-known L-type channel blocker, effectively inhibited the L-type Ca2+ currents but not the Na+ current. Our finding may explain that diclofenac causes the CV risk by the inhibition of L-type Ca2+ channel, leading to the impairment of E-C coupling in cardiac myocytes.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; Calcium Channels, L-Type ; Diclofenac ; Heart ; Heart Failure ; Ibuprofen ; Muscle Cells ; Myocytes, Cardiac ; Naproxen ; Nifedipine ; Patch-Clamp Techniques ; Rats