Epinephrine promotes hemostasis in rats with cyclophosphamide-induced hemorrhagic cystitis

Objectives. To evaluate the hypothesis that intravesical instillation of epinephrine would attenuate bladder hemorrhage in a rat model of cyclophosphamide (CYP)-induced hemorrhagic cystitis. Methods. Female Sprague-Dawley rats were divided into seven treatment groups: positive control (CYP, 150 mg/kg), negative control (epinephrine, 10 mu g/mL), intravesical instillation of normal saline (vehicle) and epinephrine (2.5, 5, and 10 mu g/mL), and intraperitoneal administration of mesna (50 mg/kg). Rats were killed on days 1, 2, and 3, and the urinary bladders were removed, weighed, and evaluated by gross and histologic analysis. Vesical vascular permeability was determined by wet bladder weight and Evan's blue dye absorbance. Results. Cyclophosphamide administration induced severe hemorrhagic cystitis with marked edema, hemorrhage, and inflammation. All three epinephrine-treated groups had marked attenuation of hemorrhagic cystitis compared with the positive and negative control and mesna-treated groups. Epinephrine was also associated with significant inhibition of tissue edema, indicating decreased vesical vascular permeability. Conclusions. In this rat model of CYP-induced hemorrhagic cystitis, intravesical instillation of epinephrine inhibited edema, hemorrhage, and inflammation.