In the field of bypass surgery, the angiosome concept seems unimportant, at least in non-ESRD cases. The location and extent of ischaemic wounds as well as co-morbidities may be more relevant than the angiosome in terms of wound healing.

We evaluated the pharmacological characteristics of (R)-2-(2-aminothiazol-4-yl)-4Ј-{2-[(2-hydroxy-2-phenylethyl)amino]-ethyl} acetanilide (YM178). YM178 increased cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing human ␤ 3 -adrenoceptor (AR). The half-maximal effective concentration (EC 50 ) value was 22.4 nM. EC 50 values of YM178 for human ␤ 1 -and ␤ 2 -ARs were 10,000 nM or more, respectively. The ratio of intrinsic activities of YM178 versus maximal response induced by isoproterenol (nonselective ␤-AR agonist) was 0.8 for human ␤ 3 -ARs, 0.1 for human ␤ 1 -ARs, and 0.1 for human ␤ 2 -ARs. The relaxant effects of YM178 were evaluated in rats and humans bladder strips precontracted with carbachol (CCh) and compared with those of isoproterenol and 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP-12177A) (␤ 3 -AR agonist). EC 50 values of YM178 and isoproterenol in rat bladder strips precontracted with 10 Ϫ6 M CCh were 5.1 and 1.4 M, respectively, whereas those in human bladder strips precontracted with 10 Ϫ7 M CCh were 0.78 and 0.28 M, respectively. In in vivo study, YM178 at a dose of 3 mg/kg i.v. decreased the frequency of rhythmic bladder contraction induced by intravesical filling with saline without suppressing its amplitude in anesthetized rats. These findings suggest the suitability of YM178 as a therapeutic drug for the treatment of symptoms of overactive bladder such as urinary frequency, urgency, and urge incontinence.

Arteriovenous (AV) access failure resulting from venous neointimal hyperplasia is a major cause of morbidity in patients with ESRD. To understand the role of chronic kidney disease (CKD) in the development of neointimal hyperplasia, we created AV fistulae (common carotid artery to jugular vein in an end-to-side anastomosis) in mice with or without CKD (renal ablation or sham operation). At 2 and 3 wk after operation, neointimal hyperplasia at the site of the AV anastomosis increased 2-fold in animals with CKD compared with controls, but cellular proliferation in the neointimal hyperplastic lesions did not significantly differ between the groups, suggesting that the enhanced neointimal hyperplasia in the setting of CKD may be secondary to a migratory phenotype of vascular smooth muscle cells (VSMC). In ex vivo migration assays, aortic VSMC harvested from mice with CKD migrated significantly greater than VSMC harvested from control mice. Moreover, animals with CKD had higher serum levels of osteopontin, which stimulates VSMC migration. When we treated animals with bone morphogenic protein-7, which promotes VSMC differentiation, before creation of the AV anastomosis, the effect of CKD on the development of neointimal hyperplasia was eliminated. In summary, CKD accelerates development of neointimal hyperplasia at the anastomotic site of an AV fistula, and administration of bone morphogenic protein-7 neutralizes this effect.

the incidence of postoperative delirium in elderly patients with chronic lower-limb ischaemia was as high as 42.3%, and an age of over 70 years and critical limb ischaemia were identified as specific markers, with 14.1 times and 3.8 times the odds of suffering from delirium after bypass surgery.