Aims: 

Upon intermittent ischemia of the urinary bladder, the vessel endothelium is a primary target of the ischemia/reperfusion (I/R) injury. In interstitial cystitis (painful bladder syndrome - PBS) or in cyclophosphamide (CYP)-induced hemorrhagic cystitis, the injury is initiated at the epithelial/urothelial surface and propagates further to the interstitium, causing a potential, but secondary involvement of the microvasculature. Hence the aim of our studies was to assess and compare the microcirculatory aspects of these non-infectious forms of cystitis.

Methods: 

In male Sprague-Dawley rats, PBS was induced by intravesical instillation of protamine-sulphate (PS, 2 mg/200 ml saline for 30 min; n=6). In another group, CYP (75 mg/kg, ip) was administered 24 hr prior to the experiments (n=5). In the third group, urinary bladder ischemia was induced by temporal (60-min) occlusion of the vessels supplying the organ (n=5). The microcirculatory inflammatory reactions were investigated using fluorescence intravital microscopy, 60 min after reperfusion and 24 hr after PS instillation or CYP administration, respectively. In the control group, the bladder was instilled with saline (n=5).

Results: 

The number of rolling leukocytes increased ~3-fold in the post-capillary vessels of the urinary bladder in the PBS group and the increase in this parameter was ~5 and ~6.5-fold in CYP and IR groups, respectively. The increase in leukocyte adherence reached similar values (increased ~7-fold) in all of the challenged groups. Red blood cell velocity in the capillaries decreased in the PS and IR groups, while moderately increased in the CYP group.

Conclusions: 

Our results demonstrate that not only I/R, which is known to cause direct endothelial injury, but also PBS and CYP administration (i.e. hemorrhagic cystitis) induce inflammatory microcirculatory changes in the urinary bladder. These observations suggest a causative role for microcirculatory disturbances in the pathogenesis of PBS and hemorrhagic cystitis.

Support: 

TAMOP-4.2.1/B-09/1/KONV-2010-0005 and TAMOP-4.2.2-08/1-2008-0013