Effects of echinocandin preparations on adult rat ventricular cardiomyocytes. Preliminary results of an in vitro study.
BACKGROUND
Candida infections represent a relevant risk for patients in intensive care units resulting in increased mortality. Echinocandins have become the agents of choice for early and specific antifungal treatment in critically ill patients. Due to cardiac effects following echinocandin administration seen in intensive care unit (ICU) patients the in vitro effects of echinocandins and fluconazole on isolated cardiomyocytes of the rat were examined.


OBJECTIVE
The study was designed to investigate a possible impact of echinocandins and fluconazole in clinically relevant concentrations on the in vitro contractile responsiveness and shape of isolated rat cardiomyocytes.


METHODS
Ventricular cardiomyocytes were isolated from Lewis rats. Cardiomyocytes were cultured in the presence of all licensed echinocandin preparations and fluconazole at concentrations of 0 (control), 0.1, 1, 3.3, 10, 33 and 100 μg/ml for 90 min. Cells were stimulated by biphasic electrical stimuli and contractile responsiveness was measured as shortening amplitude. Additionally, the ratio of rod-shaped to round cells was determined.


RESULTS
Anidulafungin concentrations of 3.3 and 10 μg/ml caused a significant increase in contractile responsiveness, caspofungin showed a significant decrease at 10 μg/ml and micafungin concentrations of 3.3-33 μg/ml led to a significant increase in cell shortening. Measurement was not possible at 33 μg/ml for anidulafungin and caspofungin and at 100 μg/ml for all echinocandins due to a majority of round-shaped, non-contracting cardiomyocytes. Fluconazole showed no significant effect on cell shortening at all concentrations tested. For the three echinocandins the ratio of round-shaped, non-contracting versus rod-shaped normal contracting cardiomyocytes increased in a dose-dependent manner.


CONCLUSIONS
Echinocandins impact the in vitro contractility of isolated cardiomyocytes of rats. This observation could be of great interest in the context of antifungal treatment.
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Gießen and Marburg, Campus Gießen, Rudolf-Buchheim-Str. 7, 35392, Gießen, Germany.
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Arens
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Uhle
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Wolff
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Röhrig
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Koch
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Schulte
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Weiterer
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Henrich
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Weigand
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Schlüter
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Lichtenstern
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000633:toxicity; D002469:Cell Separation; D048430:Cell Shape; D054714:Echinocandins / Q000494:pharmacology* / Q000633:toxicity; D004558:Electric Stimulation; D015725:Fluconazole / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew
D000935:Antifungal Agents; D054714:Echinocandins; D015725:Fluconazole