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ORIGINAL RESEARCH ARTICLE

Prophylactic Intravesical Instillation of Epinephrine Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats

Yung-Chiong Chow^*,,, Stone Yang^,, Chun-Jen Huang^,, Chin-Yuan Tzen^,||, Yu-Hsien Su^,¶ and Paulus S. Wang^*,1

^* Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan, R.O.C.; Department of Urology, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C.; Mackay Medicine, Nursing, and Management College, Taipei, Taiwan, R.O.C.; Department of Anesthesiology, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C.; ^|| Department of Pathology, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C.; and ^¶ Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C.

To whom requests for reprints should be addressed at ¹ Department and Institute of Physiology, School of Medicine, National Yang-Ming University, 155 Li-Nong Street, Section 2, Shih-Pai, Taipei, 11221 Taiwan, R.O.C. E-mail: pswang{at}ym.edu.tw

The objective of this study is to investigate the potential protective effects of intravesical instillation of epinephrine in cyclophosphamide-induced hemorrhagic cystitis. In an earlier study, we have shown that epinephrine promotes hemostasis on established hemorrhagic cystitis induced by cyclophosphamide. Female Sprague-Dawley rats were divided into seven groups as follows: group 1: positive control (150 mg/kg, cyclophosphamide, i.p.), group 2: negative control (10 µ g/ml, epinephrine, intravesical), co-administration of cyclophosphamide (150 mg/kg, i.p.), group 3: saline (intravesical), groups 4–6: epinephrine (2.5, 5, and 10 µ g/ml, intravesical), and group 7: mesna (50 mg/kg, i.p.). Rats were sacrificed on 3 consecutive days and the urinary bladders were removed, weighed, and evaluated. The vesical vascular permeability was determined by wet bladder weight and Evan’s blue dye absorbance. After 24 hours of cyclophosphamide administration, severe hemorrhagic cystitis was induced with marked edema, hemorrhage, and inflammation. In the epinephrine-treated groups, symptoms of hemorrhagic cystitis (such as edema, inflammation, and hemorrhage) were reduced significantly. Intravesical instillation of epinephrine prevents edema, hemorrhage, and inflammation in rats with cyclophosphamide-induced hemorrhagic cystitis.

Key Words: hemorrhagic cystitis • cyclophosphamide • urinary bladder • epinephrine • rat

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