Excessive ethanol (EtOH) use leads to impaired memory and cognition. Using a rat model of binge-like intoxication, we tested whether elevated corticosterone (Cort) levels contribute to the neurotoxic consequences of EtOH exposure. Rats were adrenalectomized (Adx) and implanted with cholesterol pellets, or cholesterol pellets containing basal, medium or high Cort. Intragastric EtOH or an isocaloric control solution was given 3 times daily for 4 days to achieve blood alcohol levels (BALs) ranging between 200-350 mg/dl. Mean 24 hour (24-hr) plasma Cort levels were ~110 ng/ml and ~40 ng/ml in intact EtOH treated and intact control, respectively. Basal Cort replacement in EtOH-treated Adx animals animals did not exacerbate alcohol-induced neurodegeneration in the hippocampal dentate gyrus (DG) or the entorhinal cortex (EC) as observed by amino-cupric silver staining. In contrast, Cort replacement resulting in levels 2-fold higher (medium) than normal, or higher (high) in Adx-Cort-EtOH animals increased neurodegeneration. In separate experiments, pharmacological blockade of the Type II glucocortocoid (GC) receptor was initiated with mifepristone (RU38486; 0, 5, 15 mg/kg/day, i.p.). At the higher dose, mifepristone decreased the number of degenerating hippocampal DG cells in binge-EtOH treated intact animals, whereas, only a trend for reduction was observed in 15 mg/kg/day mifepristone treated animals in the EC, as determined by Fluoro Jade B staining. These results suggest that Cort in part mediates EtOH-induced neurotoxicity in the brain through activation of Type II GC receptors.
Background
Ventricular tachycardia (VT) is frequently encountered in patients with repaired and unrepaired congenital heart disease (CHD), causing significant morbidity and sudden cardiac death. Data regarding underlying VT mechanisms and optimal ablation strategies in these patients remain limited.
Objective
To describe the electrophysiologic mechanisms, ablation strategies, and long‐term outcomes in patients with CHD undergoing VT ablation.
Methods
Forty‐eight patients (mean age 41.3 ± 13.3 years, 77.1% male) with CHD underwent a total of 57 VT ablation procedures at two centers from 2000 to 2017. Electrophysiologic and follow‐up data were analyzed.
Results
Of the 77 different VTs induced at initial or repeat ablation, the underlying mechanism in 62 (81.0%) was due to scar‐related re‐entry; the remaining included four His‐Purkinje system–related macrore‐entry VTs and focal VTs mainly originating from the outflow tract region (8 of 11, 72.7%). VT‐free survival after a single procedure was 72.9% (35 of 48) at a median follow‐up of 53 months. VT‐free survival after multiple procedures was 85.4% (41 of 48) at a median follow‐up of 52 months. There were no major complications. Three patients died during the follow‐up period from nonarrhythmic causes, including heart failure and cardiac surgery complication.
Conclusion
While scar‐related re‐entry is the most common VT mechanism in patients with CHD, importantly, nonscar‐related VT may also be present. In experienced tertiary care centers, ablation of both scar‐related and nonscar‐related VT in patients with CHD is safe, feasible, and effective over long‐term follow‐up.
Computer‐generated Bazett‐corrected QT (QTcB) algorithms are common in clinical practice and can rapidly identify repolarization abnormalities, but accuracy is variable. This report highlights marked rate‐corrected QT (QTc) interval prolongation not detected by the computer algorithm. A 26‐year‐old woman with anorexia nervosa was admitted with severe hypokalemia and ventricular ectopy. Computer‐generated QTcB was 485 ms, while manual adjudication yielded a QTcB of 657 ms and a Fridericia‐corrected QT (QTcF) interval of 626 ms using digital calipers. Computer‐generated QTc intervals may aid in clinical decision‐making. However, accuracy is variable, particularly in the setting of ectopy, and requires manual verification.
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