Amiodarone-induced pulmonary fibrosis in Fischer 344 rats

Reinhart, Paul G.; Lai, Yih‐Loong; Gairola, C. Gary

doi:10.1016/0300-483x(96)03339-2

Cited by 15 publications

(15 citation statements)

References 20 publications

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“…Although collagen is the most predominant component of the lung matrix composing 10-20% of the dry weight of lung tissues (Crystal et al, 1975), we observed that MTX induced accumulation of collagen content on the alveolar wall. Interestingly, these findings are in good agreement with several other studies that exhibited an enhancement of collagen accumulation after exposure to toxic compounds, such as silica and BLM (Crystal et al, 1975;Reinhart et al, 1996;Suzuki et al, 1996;Chung et al, 2001). Taking these published papers and our results into consideration, we subsequently measured the hydroxyproline content.…”

Section: Discussionsupporting

confidence: 91%

Induction of pulmonary fibrosis by methotrexate treatment in mice lung in vivo and in vitro

et al. 2010

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-Methotrexate (MTX) has been used as the first-line disease-modifying antirheumatic drug (DMARD) in patients with early progressive rheumatoid arthritis (RA). Several severe side effects such as myelosuppression, hepato-, nephro-, and pulmonary toxicities have been reported. However, the pathogenic mechanism of MTX-induced pulmonary fibrosis is still unknown. Here, we evaluated the morphological and biological changes of the pulmonary fibrosis in mice treated with MTX. Three, four and five weeks after consecutive administration of MTX (3 mg/kg/day), hydroxyproline content in the lung tissues increased significantly to about 2 times higher that of the control level. This result closely reflected to the results of hematoxylin and eosin (HE) and Azan stains. Immunohistochemical analysis revealed that MTX treatment resulted in a decrease of alveolar epithelial cells and an increase of fibroblast cells in the mouse lung tissues. When we examined the effects of MTX on primary mouse alveolar epithelial cell (MAEC) and mouse lung fibroblast (MLF) survival in vitro, the efficiency of MTX-induced cytotoxicity and apoptosis in MAEC was more sensitive than MLF cells. Thus, our results indicate that the administration of MTX by an oral route could induce a fibrotic response with cell dysfunction of the alveolar epithelium by which MTX-induced apoptosis. Our results thus suggest that MTX could induce alveolar epithelial cell injury and resulted in the loss of integrity of the alveolar-capillary barrier basement membranes followed by the recruitment and proliferation of myofibroblasts with the deposition of collagens.

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Section: Discussionsupporting

confidence: 91%

Induction of pulmonary fibrosis by methotrexate treatment in mice lung in vivo and in vitro

et al. 2010

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“…Endotracheal administration of amiodarone is not recommended because of its local irritating effects. 69,70 Amiodarone carries a class IIb recommendation for pulseless ventricular tachycardia or fibrillation ( Table 2). 5…”

Section: Amiodaronementioning

confidence: 99%

Pharmacotherapy Considerations in Advanced Cardiac Life Support

2006

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Cardiac arrest and sudden cardiac death remain major causes of mortality. Early intervention has been facilitated by emergency medical response systems and the development of training programs in basic life support and advanced cardiac life support (ACLS). Despite the implementation of these programs, the likelihood of a meaningful outcome in many life-threatening situations remains poor. Pharmacotherapy plays a role in the management of patients with cardiac arrest, with new guidelines for ACLS available in 2005 providing recommendations for the role of specific drug therapies. Epinephrine continues as a recommended means to facilitate defibrillation in patients with pulseless ventricular tachycardia or ventricular fibrillation; vasopressin is an alternative. Amiodarone is the primary antiarrhythmic drug that has been shown to be effective for facilitation of defibrillation in patients with pulseless ventricular tachycardia or fibrillation and is also used for the management of atrial fibrillation and hemodynamically stable ventricular tachycardia. Epinephrine and atropine are the primary agents used for the management of asystole and pulseless electrical activity. Treatment of electrolyte abnormalities, severe hypotension, pulmonary embolism, acute ischemic stroke, and toxicologic emergencies are important components of ACLS management. Selection of the appropriate drug, dose, and timing and route of administration are among the many challenges faced in this setting. Pharmacists who are properly educated and trained regarding the use of pharmacotherapy for patients requiring ACLS can help maximize the likelihood of positive patient outcomes.

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“…Conversely, inflammation and fibrosis have been induced by the i.t. administration of AD to hamsters (Cantor et al, 1984;Daniels et al, 1989;Wang et al, 1992;Blake and Reasor, 1995a) and rats (Reinhart et al, 1996), but this method lacks the phospholipidosis induced by chronic oral AD administration.…”

Section: Tnf-α Is Important In Various Ways Including Induction Of Imentioning

confidence: 99%

“…However, since the role of phospholipidosis in the development of AIPT is in question, and inflammation and fibrosis are the more damaging and life-threatening aspects of the toxicity, the i.t. route of administration is currently favored in animals studies of AIPT (Reinhart et al, 1996;Reinhart and Gairola, 1997;Card et al, 1999).…”

Section: Tnf-α Is Important In Various Ways Including Induction Of Imentioning

confidence: 99%

“…(Lindenschmidt et al, 1986). Intratracheal Models of AIPT have been developed in hamsters (Cantor et al, 1984;Daniels et al, 1989;Wang et al, 1992;Rafeiro et al, 1994;Leeder et al, 1994;Blake and Reasor, 1995a) and rats (Reinhart et al, 1996;Reinhart and Gairola, 1997) in an attempt to elucidate the mechanisms by which this disorder develops. Intratracheal instillation of AD leads to an inflammatory reaction in hamsters (Blake and Reasor, 1995a) and a fibrotic reaction in hamsters (Cantor et al, 1984;Blake and Reasor, 1995b) and rats (Reinhart et al, 1996).…”

Section: Tnf-α Is Important In Various Ways Including Induction Of Imentioning

confidence: 99%

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Amiodarone-induced pulmonary toxicity in F344 rats

Taylor¹

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Amiodarone-Induced Pulmonary Toxicity in F344 Rats. Michael D. TaylorAmiodarone (AD) is gaining support as a first-line antiarrhythmic drug despite its potentially fatal pulmonary toxicity involving inflammation and fibrosis. The goals of this study were to develop and characterize a rat model of amiodarone-induced pulmonary toxicity (AIPT). A protocol was developed in which male F344 rats were instilled intratracheally (i.t.) with AD (6.25 mg/kg with a 3.125 mg/ml solution) in sterile water or the sterile water vehicle on days 0 and 2, a protocol that led to the development of pulmonary fibrosis on day 28 in the AD-treated animals. Bronchoalveolar lavage (BAL) resulted in the increased recovery of alveolar macrophages, neutrophils, and eosinophils from i.t. AD-treated rats. The BAL cells recovered from AD-treated rats at day 3 produced more integrated phorbol-myristate-acetate stimulated luminol-dependent chemiluminescence over 20 minutes than BAL cells from control rats. These findings indicate that this model exhibits a transient pulmonary inflammation, with the potential for elevated oxidant production in the lungs, and subsequent pulmonary fibrosis. Also, serum levels of surfactant protein-D, a protein normally found in the lungs, was elevated in the serum of i.t. AD-treated rats, and is proposed as a biomarker for the toxicity. However, attempts to elucidate the cytokine signaling behind the inflammatory events were unsuccessful. It was discovered that AD instillation produces a rapid and massive damage to the alveolar-capillary barrier, and cellular death or damage to lung airway and parenchymal cells. This pathology is not consistent with that found in human AIPT. AD in solution was found to be at least partly in the form of a free radical, and capable of generating hydroxyl radicals. An attempt to modulate the toxicity of i.t. AD by incorporating water-soluble antioxidants in the drug solution was unsuccessful, and might have exacerbated the condition. No consistent evidence for deiodination of AD in solution was found, leaving the mechanism and significance of free radical generation by AD undetermined.iii

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Amiodarone-induced pulmonary fibrosis in Fischer 344 rats

Cited by 15 publications

References 20 publications

Induction of pulmonary fibrosis by methotrexate treatment in mice lung in vivo and in vitro

Induction of pulmonary fibrosis by methotrexate treatment in mice lung in vivo and in vitro

Pharmacotherapy Considerations in Advanced Cardiac Life Support

Amiodarone-induced pulmonary toxicity in F344 rats

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