Overactivity and structural changes in the chronically ischemic bladder

Purpose: Our aim was to study the effect of chronic ischemia on bladder con traction and detrusor smooth muscle reactivity. The relationship between st ructural damage and functional changes in the chronically ischemic bladder was also investigated. Material and Methods: Male New Zealand White rabbits were divided into arte rial injury (AI), hypercholesterolemia (Hch) and control groups. The AI gro up (n = 18) underwent balloon endothelial injury of the iliac arteries and received a 0.5% cholesterol diet. The Hch group (n = 8) received a 0.5% cho lesterol diet alone. The control group (n = 8) received a regular diet. Aft er 16 weeks, iliac artery and bladder wall blood flows were recorded. Cysto metrograms and arteriography were obtained and bladder tissues were process ed for isometric tension measurement in the organ bath and for histological evaluation. Results: At 16 weeks, blood flow through the iliac arteries was significant ly reduced in the Al group compared with the Hch and control groups. In the Al group, 8 animals developed severe bladder ischemia (SBI) defined as gre ater than 60% decrease in bladder blood flow, 7 animals developed moderate bladder ischemia (MBI) defined as 40 to 60% decrease in bladder blood flow, and 3 animals failed to develop significant bladder ischemia (<40% decreas e in bladder blood now). In the control animals, bladder blood flow increas ed prior to contraction, decreased during contraction and rebounded to base line levels after contraction. In animals with MBI and SBI, the increase in bladder blood flow prior to contraction and the rebound of blood flow afte r contraction, both seen in control animals, were diminished. Detrusor over activity (significant increase in the frequency of spontaneous bladder cont ractions) was observed in the MBI group and impaired bladder contraction in the SBI group. In the organ bath, bladder strips from the MBI group demons trated increased contractile response to carbachol and electrical field sti mulation (EFS) while bladder strips from the SBI group showed impaired cont ractility. Hch alone produced only short-lived ischemia during bladder cont raction and caused significantly lesser functional changes compared with th ose seen in MBI. Histological examination showed atherosclerotic occlusion in the iliac arteries and bladder microcirculation and marked disruption of urothelium in the MBI and SBI groups. Severe fibrosis was seen in bladder tissue from the SBI group, moderate fibrosis in tissue from the MBI group a nd mild fibrosis in tissue from the Hch group. Conclusions: Our studies show that chronic MBI is associated with detrusor overactivity and increased smooth muscle contractility to carbachol and EFS while chronic SBI is associated with impaired detrusor contraction The mec hanism of chronic ischemia-induced bladder dysfunction is not known and may involve multiple physiologic and structural changes in the bladder nerves, receptors and contractile components. Our studies suggest that ischemia-in duced structural damage in the urothelium and possible chronic exposure of the underlying tissue and nerves to the urine may also play a role in MBI-i nduced detrusor overactivity. SBI-induced impairment of bladder contraction may involve, in part, extensive fibrosis and loss of bladder smooth muscle . Histopathophysiologic changes in bladder tissue from our MBI model are si milar to those seen in patients with detrusor instability, suggesting that chronic ischemia may play a role in the development of idiopathic detrusor instability.