title: Cardiac response to centrally administered echinocandin antifungals.
abstract: OBJECTIVE
  The purpose of this study was to determine the effect of the echinocandin antifungals on the cardiac system, including cardiac output, blood pressure and heart rate, when administered in an in-vivo model.
  
  
  METHODS
  The echinocandin antifungals were administered via central line to male Sprague-Dawley rats. Cardiac imaging and functional measurements were made using a high-resolution in-vivo imaging system. Statistical comparisons of the experimental antifungals versus saline control were made using a Student's t-test.
  
  
  RESULTS
  In cardiac output (CO) measurements, caspofungin was associated with a bimodal distribution in results at 3 mg/kg. Those with little response, termed 'non-vulnerable' animals (n = 3) had no significant change in CO from baseline (-4.6 ± 10.7%). Other animals, termed 'vulnerable' animals (n = 3 at 3 mg/kg and those dosed at 6 mg/kg (n = 6)), experienced greater than 60% decrease in CO (-66.4 ± 13.1% at 3 mg/kg and -62.9 ± 13.0% at 6 mg/kg, P < 0.05). A dose of 5 mg/kg anidulafungin was associated with no significant changes in CO (-16.1 ± 26%), while 11.5 mg/kg decreased CO by 62.7 ± 19.4% from baseline (P < 0.05). With micafungin 1 mg/kg and 5 mg/kg doses, changes in CO were not significant (-16.7 ± 2.1% and -18.2 ± 1.9%, respectively).
  
  
  CONCLUSIONS
  These studies provide substantial evidence to support ex-vivo Langendorff and in-vitro mitochondrial studies demonstrating a similar pharmacological event. Clinical reports of similar effects also support these findings.
authors.affiliation: Pharmacy Practice, University of Mississippi School of Pharmacy, Jackson, MS, USA.|Faculty, University of Mississippi Schools Medicine-Infectious Diseases, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Kayla R
authors.initials: KR
authors.lastname: Stover
authors.affiliation: Clinical Pharmacy Manager, St. Dominic-Jackson Memorial Hospital, Jackson, MS, USA.|Faculty, University of Mississippi Schools Medicine-Infectious Diseases, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Cleary
mesh_terms: D000077612:Anidulafungin; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D000077336:Caspofungin; D054714:Echinocandins / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D055666:Lipopeptides / Q000008:administration & dosage; D008297:Male; D000077551:Micafungin; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077612:Anidulafungin; D000077336:Caspofungin; D000077551:Micafungin
keywords: cardiac output; cardiac toxicity; echinocandin; echocardiography; ultrasound