Literature DB >> 15286197

Channelling the Emperor: what really killed Napoleon?

Francesco Mari1, Elisabetta Bertol, Vittorio Fineschi, Steven B Karch.   

Abstract

Arsenic was present in Napoleon's hair before he arrived on Saint Helena and the findings at necropsy are consistent only with the diagnosis of ulcerating, regionally invasive, gastric carcinoma. The question of whether Napoleon died of, or merely with, arsenic poisoning is illuminated by developments in the treatment of promyelocytic leukaemia. Arsenic trioxide induces remission in many, but treatment can be complicated by QT prolongation, torsades de pointes and sudden death. At clinically relevant concentrations, arsenic blocks both I(Kr) and I(ks) channels and, at the same time, activates I(K-ATP) channels. The balance of these forces is easily disrupted, and QT prolongation is worsened by hypokalaemia. Napoleon was chronically treated with tartar emetic for gastrointestinal symptoms, and the day before he died he was given a huge dose of calomel (mercurous chloride) as a purgative. Both treatments would have caused potassium wastage. In addition, the Emperor was being treated with a decoction containing 'bark'-presumably 'Jesuit's bark'. The quinine in Jesuit's bark is another cause of QT prolongation. It is likely that the immediate cause of the Emperor's death was torsades de pointes, brought on by chronic exposure to arsenic and a medication error.

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Year:  2004        PMID: 15286197      PMCID: PMC1079564          DOI: 10.1177/014107680409700812

Source DB:  PubMed          Journal:  J R Soc Med        ISSN: 0141-0768            Impact factor:   18.000


  13 in total

1.  Voltage-dependent profile of human ether-a-go-go-related gene channel block is influenced by a single residue in the S6 transmembrane domain.

Authors:  Jose A Sănchez-Chapula; Tania Ferrer; Ricardo A Navarro-Polanco; Michael C Sanguinetti
Journal:  Mol Pharmacol       Date:  2003-05       Impact factor: 4.436

2.  Elemental contents in Napoleon's hair cut before and after his death: did Napoleon die of arsenic poisoning?

Authors:  Xilei Lin; D Alber; R Henkelmann
Journal:  Anal Bioanal Chem       Date:  2004-02-17       Impact factor: 4.142

3.  Arsenic in blood and urine of forest workers as indices of exposure to cacodylic acid.

Authors:  S L Wagner; P Weswig
Journal:  Arch Environ Health       Date:  1974-02

4.  Environmental variation of arsenic levels in human blood determines by neutron activation analysis.

Authors:  K Heydorn
Journal:  Clin Chim Acta       Date:  1970-05       Impact factor: 3.786

5.  Functional identification of ion binding sites at the internal end of the pore in Shaker K+ channels.

Authors:  Jill Thompson; Ted Begenisich
Journal:  J Physiol       Date:  2003-03-28       Impact factor: 5.182

6.  Effect of arsenic trioxide on QT interval in patients with advanced malignancies.

Authors:  Jean T Barbey; John C Pezzullo; Steven L Soignet
Journal:  J Clin Oncol       Date:  2003-10-01       Impact factor: 44.544

Review 7.  Drug-induced torsades de pointes and implications for drug development.

Authors:  Robert R Fenichel; Marek Malik; Charles Antzelevitch; Michael Sanguinetti; Dan M Roden; Silvia G Priori; Jeremy N Ruskin; Raymond J Lipicky; Louis R Cantilena
Journal:  J Cardiovasc Electrophysiol       Date:  2004-04

Review 8.  Pharmacogenetic considerations in diseases of cardiac ion channels.

Authors:  Arun Anantharam; Steven M Markowitz; Geoffrey W Abbott
Journal:  J Pharmacol Exp Ther       Date:  2003-10-15       Impact factor: 4.030

9.  Unusual effects of a QT-prolonging drug, arsenic trioxide, on cardiac potassium currents.

Authors:  Benoit Drolet; Chantale Simard; Dan M Roden
Journal:  Circulation       Date:  2003-12-22       Impact factor: 29.690

10.  Direct cardiac effects of As2O3 in rabbits: evidence of reversible chronic toxicity and tissue accumulation of arsenicals after parenteral administration.

Authors:  Mei-Hwan Wu; Chun-Jung Lin; Chi-Long Chen; Ming-Jai Su; Selma Siu-Man Sun; Ann-Lii Cheng
Journal:  Toxicol Appl Pharmacol       Date:  2003-06-15       Impact factor: 4.219

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  3 in total

1.  The death of Napoleon.

Authors:  Milo Keynes
Journal:  J R Soc Med       Date:  2004-10       Impact factor: 18.000

2.  Gastric Cancer in History: A Perspective Interdisciplinary Study.

Authors:  Skender Topi; Luigi Santacroce; Lucrezia Bottalico; Andrea Ballini; Alessio Danilo Inchingolo; Gianna Dipalma; Ioannis Alexandros Charitos; Francesco Inchingolo
Journal:  Cancers (Basel)       Date:  2020-01-22       Impact factor: 6.639

3.  The gastric disease of Napoleon Bonaparte: brief report for the bicentenary of Napoleon's death on St. Helena in 1821.

Authors:  Alessandro Lugli; Fatima Carneiro; Heather Dawson; Jean-François Fléjou; Richard Kirsch; Rachel S van der Post; Michael Vieth; Magali Svrcek
Journal:  Virchows Arch       Date:  2021-03-04       Impact factor: 4.064

  3 in total

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