The antiarrhythmic amiodarone (AM) and its metabolite desethylamiodarone (Des) are known to cause AM-induced pulmonary toxicity, but the mechanisms underlying this disorder remain unclear. We hypothesized that AM might cause AM-induced pulmonary toxicity in part through the induction of apoptosis or necrosis in alveolar epithelial cells (AECs). Two models of type II pneumocytes, the human AEC-derived A549 cell line and primary AECs isolated from adult Wistar rats, were incubated with AM or Des for 20 h. Apoptotic cells were determined by morphological assessment of nuclear fragmentation with propidium iodide on ethanol-fixed cells. Necrotic cells were quantitated by loss of dye exclusion. Both AM and Des caused dose-dependent necrosis starting at 2.5 and 0.1 microg/ml, respectively, in primary rat AECs and at 10 and 5 microg/ml in subconfluent A549 cells (P < 0.05 and P < 0.01, respectively). AM and Des also induced dose-dependent apoptosis beginning at 2.5 microg/ml in the primary AECs (P < 0.05 for both compounds) and at 10 and 5 microg/ml, respectively, in the A549 cell line (P < 0.01). The two compounds also caused significant net cell loss (up to 80% over 20 h of incubation) by either cell type at drug concentrations near or below the therapeutic serum concentration for AM. The cell loss was not due to detachment but was blocked by the broad-spectrum caspase inhibitor Z-Val-Ala-Asp-fluoromethylketone. Furthermore, the angiotensin-converting enzyme inhibitor captopril (500 ng/ml) and the angiotensin-receptor antagonist saralasin (50 microg/ml) significantly inhibited both the induction of apoptosis and net cell loss in response to AM. These results are consistent with recent work from this laboratory demonstrating potent inhibition of apoptosis in human AECs by captopril (Uhal BD, Gidea C, Bargout R, Bifero A, Ibarra-Sunga O, Papp M, Flynn K, and Filippatos G. Am J Physiol Lung Cell Mol Physiol 275: L1013-L1017, 1998). They also suggested that the accumulation of AM and/or its primary metabolite Des in lung tissue may induce cytotoxicity of AECs that might be inhibitable by angiotensin-converting enzyme inhibitors or other antagonists of the renin-angiotensin system.
In critical care, the monitoring is essential to the daily care of ICU patients, as the optimization of patient's hemodynamic, ventilation, temperature, nutrition, and metabolism is the key to improve patients' survival. Indeed, the decisive endpoint is the supply of oxygen to tissues according to their metabolic needs in order to fuel mitochondrial respiration and, therefore, life. In this sense, both oxygenation and perfusion must be monitored in the implementation of any resuscitation strategy. The emerging concept has been the enhancement of macrocirculation through sequential optimization of heart function and then judging the adequacy of perfusion/oxygenation on specific parameters in a strategy which was aptly coined “goal directed therapy.” On the other hand, the maintenance of normal temperature is critical and should be regularly monitored. Regarding respiratory monitoring of ventilated ICU patients, it includes serial assessment of gas exchange, of respiratory system mechanics, and of patients' readiness for liberation from invasive positive pressure ventilation. Also, the monitoring of nutritional and metabolic care should allow controlling nutrients delivery, adequation between energy needs and delivery, and blood glucose. The present paper will describe the physiological basis, interpretation of, and clinical use of the major endpoints of perfusion/oxygenation adequacy and of temperature, respiratory, nutritional, and metabolic monitorings.
Background: There is a paucity of real-time imaging modalities available for the bronchoscopic biopsy of peripheral lung nodules. We aim to demonstrate the feasibility of the O-arm imaging system to guide real-time biopsies of peripheral lung nodules during electromagnetic navigation bronchoscopy. Methods: A retrospective review was performed at 2 academic medical centers utilizing O-arm guidance. Results: The average nodule size was 2.1×2.0 cm and were mostly solid (66%) with a positive bronchus sign (83%). O-arm imaging confirmed tool-in-lesion in all cases. The diagnostic yield was 33%. Four cases were nondiagnostic of the 6 cases performed. In these cases, necrotic tissue was the most common (75%) and showed resolution following subsequent imaging. The average 3-dimensional (3D) spin time was 23.5 seconds. The average number of 3D spins performed per case was 4.33. The average effective dose per 3D spin was 3.73 mSv. Conclusion: We have demonstrated the O-arm’s feasibility with electromagnetic navigation bronchoscopy for peripheral lung nodules. The O-arm was able to confirm tool-in-lesion in all cases which added confidence to the biopsy. Four high-resolution 3D spins per case may limit the total computed tomography effective dose. We also noted that both metal and radiation scatter were minimal when appropriate radiation safety standards were met. Although additional experience and data will be required to verify the O-arm approach for routine use, our initial experience is promising.
Right heart thrombus is rare in structurally normal heart. Here, we report a 74-year-old man with a right atrial thrombus who presented with shortness of breath.
Myeloid sarcoma should be part of the differential for acute tracheal stenosis.
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