Background: The vascular endothelium is a primary target of ischemia/reperfusion (IR) injury of the urinary bladder. In case of interstitial cystitis (painful bladder syndrome) or in cyclophosphamide-induced hemorrhagic cystitis, the injury is initiated at the epithelial/urothelial surface and propagates towards the interstitium, causing secondary involvement of the microvasculature. Hence the aim of our study was to assess and compare the microcirculatory aspects of the non-infectious forms of cystitis with that of IR-caused reactions.
Materials and methods: In male Sprague-Dawley rats, interstitial cystitis was induced by intravesical instillation of protamine sulphate (2 mg in 200 μl saline for 30 min; n = 6). In another group, cyclophosphamide (75 mg/kg, ip) was administered 24 hr prior to the experiments (n = 5). In the third group, urinary bladder ischemia was induced by 60-min occlusion of the vessels supplying the bladder (n = 5). The microcirculatory inflammatory reactions were investigated by fluorescence intravital microscopy 60 min after reperfusion and 24 hr after protamine sulphate instillation or cyclophosphamide administration, respectively. In the control group, the bladder was instilled with saline (n = 5).
Results: Rolling of leukocytes increased ~3-fold in the postcapillary vessels in the protamine sulphate-treated group and the increase in this parameter was ~5 and ~6.5-fold in cyclophosphamide and IR groups, respectively. The increase in leukocyte adherence reached similar, approx. 7-fold increase in each of the challenged groups. The red blood cell velocity in the capillaries decreased in the protamine sulphate and IR groups, while the velocity increased moderately in the cyclophosphamide-treated group.
Conclusions: Our results demonstrate that direct endothelial injury (caused by IR), as well as protamine sulphate and cyclophosphamide administrations induce inflammatory microcirculatory changes of the urinary bladder. These observations suggest a causative role for microcirculatory disturbances in the pathogenesis of interstitial cystitis and hemorrhagic cystitis as well.