title: Overactivity and structural changes in the chronically ischemic bladder.
abstract: OBJECTIVE
  Our aim was to study the effect of chronic ischemia on bladder contraction and detrusor smooth muscle reactivity. The relationship between structural damage and functional changes in the chronically ischemic bladder was also investigated.
  
  
  METHODS
  Male New Zealand White rabbits were divided into arterial injury (AI), hypercholesterolemia (Hch) and control groups. The AI group (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% cholesterol diet alone. The control group (n = 8) received a regular diet. After 16 weeks, iliac artery and bladder wall blood flows were recorded. Cystometrograms and arteriography were obtained and bladder tissues were processed for isometric tension measurement in the organ bath and for histological evaluation.
  
  
  RESULTS
  At 16 weeks, blood flow through the iliac arteries was significantly reduced in the AI group compared with the Hch and control groups. In the AI group, 8 animals developed severe bladder ischemia (SBI) defined as greater 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% decrease in bladder blood flow). In the control animals, bladder blood flow increased prior to contraction, decreased during contraction and rebounded to baseline levels after contraction. In animals with MBI and SBI, the increase in bladder blood flow prior to contraction and the rebound of blood flow after contraction, both seen in control animals, were diminished. Detrusor overactivity (significant increase in the frequency of spontaneous bladder contractions) was observed in the MBI group and impaired bladder contraction in the SBI group. In the organ bath, bladder strips from the MBI group demonstrated increased contractile response to carbachol and electrical field stimulation (EFS) while bladder strips from the SBI group showed impaired contractility. Hch alone produced only short-lived ischemia during bladder contraction and caused significantly lesser functional changes compared with those 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 and 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 mechanism 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-induced 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-induced 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 similar to those seen in patients with detrusor instability, suggesting that chronic ischemia may play a role in the development of idiopathic detrusor instability.
authors.affiliation: Department of Urology, Boston University School of Medicine and Urology Research, Boston VA Medical Center, Massachusetts 02130, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Azadzoi
authors.forename: T
authors.initials: T
authors.lastname: Tarcan
authors.forename: R
authors.initials: R
authors.lastname: Kozlowski
authors.forename: R J
authors.initials: RJ
authors.lastname: Krane
authors.forename: M B
authors.initials: MB
authors.lastname: Siroky
mesh_terms: D000818:Animals; D002908:Chronic Disease; D006439:Hemodynamics; D006937:Hypercholesterolemia / Q000473:pathology / Q000503:physiopathology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology; D011817:Rabbits; D001743:Urinary Bladder / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*