Mechanisms of Lower Urinary Tract Symptoms in Pelvic Ischemia

The etiology of lower urinary tract symptoms is poorly understood. The pathophysiology of detrusor instability, voiding dysfunction and pelvic pain in patients with non-obstructed bladder remains highly controversial. In the male, most cases of lower urinary tract symptoms are attributed to bladder outlet obstruction due to benign prostatic hyperplasia. However, urodynamic data have revealed that in approximately one third to more than one half of cases, lower urinary tract symptoms are not associated with enlarged prostate or bladder outlet obstruction. Interestingly, lower urinary tract symptoms questionnaires in women yield scores that are similar to their age-matched male counterparts. These observations imply that aging-associated sex-independent changes in bladder vasculature, nerves, smooth muscle and epithelium may play a role in the development of lower urinary tract symptoms. Epidemiologic studies have shown a close correlation between vascular occlusive disorders and the prevalence of lower urinary tract symptoms. International prostate symptom scores were found to be significantly worse in men with cardiovascular disorders than symptomatic patients without cardiovascular problems. Clinical trials have revealed a close correlation between decreased pelvic blood flow and severity of lower urinary tract symptoms in the elderly patients. Studies with experimental models of pelvic ischemia have shown that accumulation of reactive oxygen species in the ischemic bladder initiates a cascade of cellular, subcellular and molecular reactions. These reactions to ischemia appear to compromise bladder structure and function leading to neurodegeneration, smooth muscle instability, increased contractile activity, fibrosis and non-compliance. These observations collectively introduce a new concept in the pathophysiology of voiding dysfunction suggesting that pelvic ischemia may be an independent factor in the development of non-obstructed non-neurogenic overactive bladder and lower urinary tract symptoms.