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Effects of echinocandin preparations on adult rat ventricular cardiomyocytes. Preliminary results of an in vitro study.

Arens C, Uhle F, Wolff M, Röhrig R, Koch C, Schulte A, Weiterer S, Henrich M, Weigand MA, Schlüter KD, Lichtenstern C - Anaesthesist (2014)

Bottom Line: 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.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.Fluconazole showed no significant effect on cell shortening at all concentrations tested.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital of Gießen and Marburg, Campus Gießen, Rudolf-Buchheim-Str. 7, 35392, Gießen, Germany.

ABSTRACT

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.

Aim: 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.

Material and 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.

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Related in: MedlinePlus

Effect of different antifungal preparations and concentrations on cellular parameters of isolated rat cardiomyocytes. a Contractility responsiveness measured as shortening ratio (dL/L). Graphs show mean values ± standard deviation. b Single cell observation of contractility at 3.3 and 10 µg/ml versus controls. c Rounded cells (grey bars) and rod-shaped cells (white bars) were counted. d Representive micrograph of culture dish following high-dose echinocandins given in culture medium containing 10 mg/ml albumin. Middle picture: overview, top and bottom: magnified areas of overview picture. Black line depicts limits of impact area
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Fig1: Effect of different antifungal preparations and concentrations on cellular parameters of isolated rat cardiomyocytes. a Contractility responsiveness measured as shortening ratio (dL/L). Graphs show mean values ± standard deviation. b Single cell observation of contractility at 3.3 and 10 µg/ml versus controls. c Rounded cells (grey bars) and rod-shaped cells (white bars) were counted. d Representive micrograph of culture dish following high-dose echinocandins given in culture medium containing 10 mg/ml albumin. Middle picture: overview, top and bottom: magnified areas of overview picture. Black line depicts limits of impact area

Mentions: In the experiments anidulafungin concentrations of 3.3, and 10 μg/ml showed a significant increase of contractility responsiveness in contrast to 0.1 and 1 μg/ml which were not different compared to controls (Fig. 1a,b; Tab. 1). For caspofungin cell shortening was not different compared to controls for 0.1–3.3 μg/ml; however, incubation with 10 μg/ml showed a significant decrease. Micafungin concentrations of 0.1 and 1 μg/ml showed no effect in contrast to controls while incubation with 3.3–33 μg/m 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 in all analyzed concentrations.


Effects of echinocandin preparations on adult rat ventricular cardiomyocytes. Preliminary results of an in vitro study.

Arens C, Uhle F, Wolff M, Röhrig R, Koch C, Schulte A, Weiterer S, Henrich M, Weigand MA, Schlüter KD, Lichtenstern C - Anaesthesist (2014)

Effect of different antifungal preparations and concentrations on cellular parameters of isolated rat cardiomyocytes. a Contractility responsiveness measured as shortening ratio (dL/L). Graphs show mean values ± standard deviation. b Single cell observation of contractility at 3.3 and 10 µg/ml versus controls. c Rounded cells (grey bars) and rod-shaped cells (white bars) were counted. d Representive micrograph of culture dish following high-dose echinocandins given in culture medium containing 10 mg/ml albumin. Middle picture: overview, top and bottom: magnified areas of overview picture. Black line depicts limits of impact area
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3921465&req=5

Fig1: Effect of different antifungal preparations and concentrations on cellular parameters of isolated rat cardiomyocytes. a Contractility responsiveness measured as shortening ratio (dL/L). Graphs show mean values ± standard deviation. b Single cell observation of contractility at 3.3 and 10 µg/ml versus controls. c Rounded cells (grey bars) and rod-shaped cells (white bars) were counted. d Representive micrograph of culture dish following high-dose echinocandins given in culture medium containing 10 mg/ml albumin. Middle picture: overview, top and bottom: magnified areas of overview picture. Black line depicts limits of impact area
Mentions: In the experiments anidulafungin concentrations of 3.3, and 10 μg/ml showed a significant increase of contractility responsiveness in contrast to 0.1 and 1 μg/ml which were not different compared to controls (Fig. 1a,b; Tab. 1). For caspofungin cell shortening was not different compared to controls for 0.1–3.3 μg/ml; however, incubation with 10 μg/ml showed a significant decrease. Micafungin concentrations of 0.1 and 1 μg/ml showed no effect in contrast to controls while incubation with 3.3–33 μg/m 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 in all analyzed concentrations.

Bottom Line: 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.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.Fluconazole showed no significant effect on cell shortening at all concentrations tested.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital of Gießen and Marburg, Campus Gießen, Rudolf-Buchheim-Str. 7, 35392, Gießen, Germany.

ABSTRACT

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.

Aim: 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.

Material and 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.

Show MeSH
Related in: MedlinePlus