Cardiac effects of echinocandins after central venous administration in adult rats.
Antimicrob Agents Chemother. 2014 Dec 29;
Authors: Koch C, Uhle F, Wolff M, Arens C, Schulte A, Li L, Niemann B, Henrich M, Rohrbach S, Weigand MA, Lichtenstern C
Echinocandins have become the agents of choice for early and specific antifungal treatment in critically ill patients. In-vitro studies and clinical case reports revealed a possible impact of echinocandin treatment on cardiac function. The aim of our study was to evaluate echinocandin induced cardiac failure : Using an in-vivo rat model we assessed hemodynamic parameters and time to hemodynamic failure after central-venous application (Vena jugularis interna) of anidulafungin (low dose group 2.5 mg/kg bodyweight (BW), high dose group 25 mg/kg BW), caspofungin (low dose group 0.875 mg/kg BW, high dose group 8.75 mg/kg BW), micafungin (low dose group 3 mg/kg BW, high dose group 30mg/kg BW) and placebo (0.9% sodium chloride). Left ventricular heart tissue was collected to determine mitochondrial enzyme activity via spectrophotometric measurements. mRNA expression of transcriptional regulators and primary mitochondrial transcripts, mtDNA content, and citrate synthase activity were also explored. Animals receiving high dose anidulafungin or caspofungin showed immediate decrease in hemodynamic function. All of the subjects in these groups died during the observation period. Each animal of the untreated control group survived (p<0.001). Hemodynamic failure was not noticed in anidulafungin and caspofungin low dose groups. micafungin had no impact on cardiac function. Analyzing mitochondrial enzyme activity and mitochondrial transcripts we found no association between echinocandin administration and the risk for hemodynamic failure. Further experimental studies are needed to elucidate the underlying mechanisms involved in cardiotoxic echinocandin effects. In addition randomized, controlled clinical trials are needed to explore the clinical impact of echinocandin treatment in critical ill patients.
PMID: 25547351 [PubMed - as supplied by publisher]