Prophylactic and therapeutic carboprost tromethamine bladder irrigation in rats with cyclophosphamide-induced hemorrhagic cystitis

Abstract

Recently, prostaglandins have been shown to be effective agents for the treatment of cyclophosphamide-induced hemorrhagic cystitis. Among the prostaglandins studied is carboprost tromethamine, a PGF2a analog. To determine the effectiveness of carboprost tromethamine therapy on the urothelium, we induced hemorrhagic cystitis in 81 rats. These were divided into two treatment arms. One arm was treated prophylactically at the time of cyclophosphamide injection, and the other started treatment only after hemorrhagic cystitis was established. Animals were divided equally into groups receiving 0, 0.4, 0.8, and 1.6 mg.% carboprost tromethamine in 0.9% normal saline by continuous bladder irrigation. All bladders were examined grossly for edema and hemorrhage, then histologically for mucosal ulceration, congestion, and perivascular hemorrhage. Results from the prophylactic arm, as compared to those for controls, revealed that all groups except those treated only with 0.9% normal saline had a lower incidence of hemorrhagic cystitis (p less than 0.05). In the established hemorrhagic cystitis arm, the group treated with 1.6 mg.% carboprost tromethamine showed the best response (p less than 0.05), whereas the group treated with 0.9% normal saline showed the poorest response. This study reveals that hemorrhagic cystitis in the rat model may be prevented by prophylactic continuous bladder irrigation with carboprost tromethamine, whereas established hemorrhagic cystitis may be treated effectively with intravesical instillation of carboprost tromethamine. Although the mechanism of action of this prostaglandin on the urothelium is unknown, it appears grossly and histologically to decrease ulceration, perivascular hemorrhage, and congestion in the mucosa and submucosa.