Partial Outlet Obstruction in Rabbits: Duration Vs Severity: A Review

Robert M. Levin, Catherine Schuler, Connor Callaghan, Robert E Leggett


Background: Obstructive bladder dysfunction (OBD) is a common medical problem. More than 80% of males older than 50 years of age have varying degrees of OBD secondary to benign prostatic hyperplasia. Methods: For the studies presented in this review article, we utilized a rabbit model of partial outlet obstruction in which we surgically place a silk ligature loosely around the catheterized urethra of a male rabbit for various periods of time. Results: Our studies to date have demonstrated that OBD is initiated by four specific pathological processes: 1) Selective postsynaptic denervation and defective neurohumoral transmission; 2)  mitochondrial damage and intracellular metabolic dysfunction; 3) sarcoplasmic reticulum (SR) damage; and 4) calcium dysregulation resulting in an increase in basal intracellular free calcium and the activation of specific calcium-activated proteases and lipases. Conclusions: From the studies described in this review, we have developed the following hypothesis concerning the etiology of OBD in both our rabbit model of OBD and OBD in men: (A) The shift from compensated bladder function to mild decompensation is primarily due to intracellular calcium overload of the smooth muscle cells and the activation of proteolytic and lipolytic enzymes. (B) The shift from mild obstructive bladder dysfunction through severe dysfunction is primarily due to oxidative stress and the generation of oxidative free radicals resulting in oxidative damage to the same cellular and subcellular membrane systems as described above.


Bladder; Ischemia; Oxidative Stress; Rabbit; Calcium Overload

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