title: Cardiac toxicity of some echinocandin antifungals.
abstract: BACKGROUND
  Unexplained cardiovascular decompensation has been observed during central venous administration of some echinocandins.
  
  
  OBJECTIVE
  The purpose of this study was to assess cardiac toxicity associated with the echinocandins.
  
  
  METHODS
  Isolated rat hearts (Langendorff model) were perfused with anidulafungin (ANID), caspofungin (CASP), or micafungin (MICA) at exposures of 1, 4, and 10 times therapeutic concentrations. Changes in left ventricular contractility with experimental exposure were compared to control, and histologic and transmission electron microscopy (TEM) examinations of tissue were performed.
  
  
  RESULTS
  Mean concentrations of ANID (10 - 80 µg/ml) and CASP (6 - 48 µg/ml) were associated with significant decreases in contractility (-77.1 ± 9.4% and -40.6 ± 15.6%, respectively; p < 0.05). MICA was associated with an increase in contractility (13.6 ± 2.8%, p = NS). On TEM, samples exposed to ANID and CASP had enlarged mitochondria and disintegrating myofibrils. Samples exposed to MICA showed some enlarged mitochondria.
  
  
  CONCLUSIONS
  Mean concentrations of ANID and CASP were associated with statistically significant decreases in left ventricular contractility at concentrations that may be achievable in humans after peripheral administration, while MICA caused no change. TEM studies suggest this may be a result of mitochondrial damage. Caution may be warranted with central administration of these agents to patients with preexisting cardiac dysfunction.
authors.affiliation: University of Mississippi, Pharmacy Practice , 2500 North State Street, Jackson, MS 39216 , USA kstover@umc.edu.
authors.forename: Kayla R
authors.initials: KR
authors.lastname: Stover
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Farley
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Kyle
authors.forename: John D
authors.initials: JD
authors.lastname: Cleary
mesh_terms: D000077612:Anidulafungin; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000633:toxicity*; D000077336:Caspofungin; D004305:Dose-Response Relationship, Drug; D054714:Echinocandins / Q000008:administration & dosage / Q000633:toxicity*; D055666:Lipopeptides / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D000077551:Micafungin; D046529:Microscopy, Electron, Transmission; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000473:pathology; D009200:Myocardial Contraction / Q000187:drug effects*; D009210:Myofibrils / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018675:Toxicity Tests
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077612:Anidulafungin; D000077336:Caspofungin; D000077551:Micafungin