Cardiovascular toxicology
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Cardiovascular toxicology · Dec 2014
The correlation between prolonged corrected QT interval with the frequency of respiratory arrest, endotracheal intubation, and mortality in acute methadone overdose.
Corrected QT interval (QTc) prolongation is long considered as a predisposing factor for the occurrence of torsade de pointes (TdP) and sudden cardiac arrest in methadone maintenance treatment. We aimed to elucidate the correlation between QTc prolongation and in-hospital death, respiratory arrest, and endotracheal intubation in acute methadone-intoxicated patients presenting to the emergency department and to assess the value of QTc in predicting these outcomes. A prospective cross-sectional study with a convenience sample of patients with acute methadone overdose was done. ⋯ The receiver operating characteristics curves drawn to show the ability of QTc to predict death, intubation, and respiratory arrest showed thresholds of 470, 447.5, and 450 ms with sensitivity (95 % CI) and specificity (95 % CI) of 87.5 (47.3-99.7), 86.8 (74.7-94.5), and 77.3 (62.2-88.5), respectively. Our study showed that QTc is a potential predictor for adverse outcomes related to acute methadone intoxication. The correlations shown in this study between triage-time QTc and in-hospital respiratory arrest or intubation in methadone overdose may be of clinical value, whether these outcomes are hypothesized to be a reflection of background TdP or intoxication severity.
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Cardiovascular toxicology · Dec 2014
Serum-glucocorticoid regulated kinase 1 regulates macrophage recruitment and activation contributing to monocrotaline-induced pulmonary arterial hypertension.
Sustained inflammation is associated with pulmonary vascular remodeling and arterial hypertension (PAH). Serum-glucocorticoid regulated kinase 1 (SGK1) has been shown to participate in vascular remodeling, but its role in inflammation-associated PAH remains unknown. In this study, the importance of SGK1 expression and activation was investigated on monocrotaline (MCT)-induced PAH, an inflammation-associated experimental model of PAH used in mice and rats. ⋯ EMD638683 treatment suppressed macrophage infiltration and inhibited the proliferation of pulmonary arterial smooth muscle cells (PASMCs) in the lungs of rats with MCT-induced PAH. Co-culture of bone marrow-derived macrophages (BMDMs) from wild-type (WT) mice promoted proliferation of PASMC in vitro, whereas BMDMs from either SGK1 knockout mice or WT mice with EMD638683 treatment failed to induce this response. Collectively, the present results demonstrated that SGK1 is important to the regulation of macrophage activation that contributes to the development of PAH; thus, SGK1 may be a potential therapeutic target for the treatment of PAH.