title: Acute length adaptation and adjustable preload in the human detrusor.
abstract: The biomechanical properties of length adaptation and adjustable preload have been previously identified in detrusor smooth muscle in animal models. This in vitro study aims to show that human detrusor smooth muscle exhibits length adaptation and adjustable preload tension which could play an important role in both overactive bladder and detrusor underactivity.
  
  
  
  In order to demonstrate length adaptation, human detrusor smooth muscle strips are stretched and contracted beyond an optimum length and then contracted three times at the previous optimum length to determine if maximum active tension could be re-established. To demonstrate adjustable preload (Tap ), human detrusor smooth muscle strips are subjected to a pre-defined loading-unloading (strain softening) sequence to reduce preload. Then, tissues are contracted and the sequence is repeated to determine if this active process restored preload.
  
  
  
  Nine patients (average age, 62) provide tissue: 89% are men with urothelial carcinoma and a minority (22%) also have neurogenic bladder dysfunction. In the length adaptation protocol, contractions show progressive increases in active tension (P < 0.05). In the Tap protocol, a significant amount of preload is lost to strain softening (P < 0.05) and is restored after active contraction (P = 0.50). Exposure to the rho-kinase inhibitor, H-1152, prevents the restoration of preload (P < 0.05).
  
  
  
  This study demonstrates that human detrusor smooth muscle displays both length adaptation and Tap . Furthermore, Tap may be regulatable through a rho-kinase pathway. These biomechanical processes may be important in the pathophysiology of both overactive bladder and detrusor underactivity. Neurourol. Urodynam. 35:792-797, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Surgery/Division of Urology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Colhoun
authors.affiliation: Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University School of Engineering, Richmond, Virginia.
authors.forename: John E
authors.initials: JE
authors.lastname: Speich
authors.affiliation: Department of Surgery/Division of Urology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: MaryEllen T
authors.initials: MT
authors.lastname: Dolat
authors.affiliation: Department of Surgery/Division of Urology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Habibi
authors.affiliation: Department of Surgery/Division of Urology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Georgi
authors.initials: G
authors.lastname: Guruli
authors.affiliation: Departments of Biochemistry and Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Ratz
authors.affiliation: Department of Emergency Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Barbee
authors.affiliation: Department of Surgery/Division of Urology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Klausner
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000222:Adaptation, Physiological / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: C459092:2-methyl-1-((4-methyl-5-isoquinolinyl)sulfonyl)homopiperazine; D004791:Enzyme Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases
keywords: compliance; overactive; rho-kinase; urinary bladder