Cardiac response to centrally administered echinocandin antifungals

OBJECTIVES: 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. KEY FINDINGS: 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.