Abstract
BACKGROUND: The deleterious effects of chronic ischemia on bladder function have been extensively studied; however, evaluation and characterization of the effects of acute ischemia and hypoxia are lacking. The present study examined pig and human detrusor smooth muscle (DSM) strips, in combination with an isolated perfused working pig bladder model to evaluate the relationship between transient ischemia and bladder function. METHODS: Organ bath and myographic studies were performed using pig and human DSM strips exposed to starvation/hypoxia conditions. Analogous conditions were then recreated in the ex vivo bladder preparation. Filled bladders were then treated with intravascular carbachol to induce contraction and subsequent void. An intravesical transducer continuously monitored changes in bladder pressure, while a tissue pO(2) monitor analyzed changes in oxygenation. RESULTS: After 120 min in starved/hypoxic conditions, both pig and human DSM strips demonstrated significantly increased resting tone, with a greater than two-fold increase in force over control. This was effectively blocked with atropine. DSM strips also demonstrated significantly weaker contractions; however, contractile force was nearly recovered following 15-min exposure to replete/oxygenated buffer. In the ex vivo bladder preparation, filling under ischemic conditions yielded a 225% increase in end-fill vesical pressures (P(ves)) compared to controls. End-fill P(ves) returned to baseline with reperfusion during a subsequent filling cycle. CONCLUSIONS: Transient ischemia/hypoxia leads to an acute increase in tone in both DSM strips and ex vivo pig bladder. Remarkably, the effect is reversible with re-perfusion and may be blocked with anticholinergics, suggesting a relationship between acute ischemia and increased local acetylcholine release.