Ischemia of the bladder, as the cause of its dysfunction after acute urinary retention

Kirpatovskiy V.I., Plotnikov E.Yu., Mudraya I.S., Hromov R.A., Revenko S.V., Zorov D.B.

Experiments were carried out on 30 female albino rats. 10 intact rats served as controls, in 20 rats acute urinary retention (AUR) by placing a microvascular clamp on proximal urethra for 4 hours was caused. In rats with AUR blood supply of the bladder was deteriorated, as in urinary retention, and a day after its recovery, which was established by spectral analysis of the impedance. Reduction of intramural blood flow was accompanied by activation of production of active oxygen radicals in the endothelium of the intramural vessels, the epithelium of the mucosa and detrusor smooth muscle cells, which was indicated by the enhance of the dichlorofluorescein probe fluorescence in laser confocal microscopy. These changes persisted and even intensified a day after the elimination of AUR by severe infiltration of the bladder wall cells, presumably leucocytes, producing reactive oxygen species. Severe degenerative changes in epithelial cells were revealed. Confocal microscopy with a tetramethylrhodamine mitochondrial probe showed a decrease in its fluorescence day after AUR in the mitochondria cells of the mucous membrane cells, and detrusor muscle cells, suggesting a decrease in their ATP-synthesizing capacity. The findings show impaired blood supply to the bladder caused by AUR, which induces oxidative damage to cell structures. The result is damage to the epithelial lining of the mucosus membrane and the violation of its barrier features with development of interstitial cell infiltration, as well as mitochondrial damage and the development of energy-deficient state of the detrusor smooth muscle cells. Identified key role of ischemia and oxidative stress in the development of bladder dysfunction after AUR provides a basis for studying the feasibility of introducing pharmaceuticals with vascular trophic and antioxidant activity in the treatment regimen of patients with BPH and AUR. 

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