“…It is our hypothesis that the mechanisms by which I/R induced bladder dysfunction is through activation of speci¢c hydrolytic enzymes including calpain (Ca 2þ -activated protease) and phospholipase A 2 (Ca 2þ -activated lipase) with subsequent damage to intracellular organelles such as the mitochondria and sarcoplasmic reticulum and via generation of free radicals and subsequent membrane lipid peroxidation [Lin et al, 1995b[Lin et al, , 1996Buttyan et al, 1997;Zhao et al, 1997;Hass and Levin, 2003].We now have direct evidence that partial outlet obstruction induces focal sites of hypoxia within the bladder smooth muscle [Ghafar et al, 2002;Levin et al, 2003]. The concept is that whenever the bladder contracts, the bladder wall compression reduces the blood £ow to the detrusor smooth muscle and results in areas of hypoxia, which then recovers to control levels during bladder ¢lling [Greenland et al, 1997[Greenland et al, , 2000.…”