Cardiac response to centrally administered XXXX antifungals.

@entity1331 @entity25928 @entity998 @entity5637 @entity35 @entity11794
OBJECTIVES: The purpose of this study was to determine the effect of the @entity5637 antifungals on the cardiac system, including @entity998 , blood pressure and heart rate, when administered in an in-vivo model. METHODS: The @entity5637 antifungals were administered via central line to male @entity35 . 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 @entity998 (CO) measurements, @entity11794 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 @entity25928 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 @entity1331 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.
