THE CARDIOPULMONARY, EICOSANOID, AND TISSUE MICROANATOMIC EFFECTS OF FLUCONAZOLE DURING GRADED BACTEREMIA

Imidazole compounds have been shown to be beneficial in systemic sepsi s and inflammation. The purpose of this study was to delineate the eff ects of fluconazole on systemic hemodynamics and on microanatomy of th e heart, lung, liver, and kidney parenchyma of swine during graded bac teremia. Eighteen adult swine were studied in three groups: 1), anesth esia control; 2), septic control (Aeromonas hydrophila, 10(9)/mL, infu sed i.v. for 4 h); 3) fluconazole (fluconazole, 30 mg/kg i.v., followe d by A. hydrophila infusion). After 4 h of graded bacteremia, autopsy was performed. Compared with the septic control group, cardiac index, oxygen delivery, and oxygen consumption were reduced significantly aft er fluconazole pretreatment, and mixed venous hemoglobin oxygen satura tion (SVO2) and oxygen extraction were increased. Plasma thromboxane A (2) and leukotriene levels were not affected by fluconazole. Computeri zed digital image analysis of the liver, heart, and kidney specimens r evealed no statistically significant differences between the septic co ntrol group and fluconazole-pretreated animals. In the lung specimens, preinfusion of fluconazole decreased alveolar wall thickness in septi c swine (anesthesia control group: 8.15 x 10(-3) +/- 1.3 x 10(-3)mm ve rsus septic control group: 9.9 x 10(-3) +/- 1.3 x 10(-4) versus flucon azole group: 6.8 x 10(-3) +/- 1.6 x 10(-3); p less than or equal to .0 5). Fluconazole pretreatment before graded bacteremia has no beneficia l effect on cardiopulmonary performance or septic tissue edema of the heart, kidney, or liver. Tissue oxygen metabolism might be down-regula ted by fluconazole. However, preinfusion of fluconazole appears to nor malize the sepsis-induced increase in pulmonary alveolar wall thicknes s. The net significance of these changes on clinical outcome is not cl ear from these data.