title: Stability of the acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats.
abstract: Time- and vehicle-related variability of bladder and urethral rhabdosphincter (URS) activity as well as cardiorespiratory and blood chemistry values were examined in the acetic acid-induced bladder irritation model in α-chloralose-anesthetized female cats. Additionally, bladder and urethra were evaluated histologically using Mason trichrome and toluidine blue staining. Urodynamic, cardiovascular and respiratory parameters were collected during intravesical saline infusion followed by acetic acid (0.5%) to irritate the bladder. One hour after starting acetic acid infusion, a protocol consisting of a cystometrogram, continuous infusion-induced rhythmic voiding contractions, and a 5 min "quiet period" (bladder emptied without infusion) was precisely repeated every 30 minutes. Administration of vehicle (saline i.v.) occurred 15 minutes after starting each of the first 7 cystometrograms and duloxetine (1mg/kg i.v.) after the 8(th). Acetic acid infusion into the bladder increased URS-EMG activity, bladder contraction frequency, and decreased contraction amplitude and capacity, compared to saline. Bladder activity and URS activity stabilized within 1 and 2 hours, respectively. Duloxetine administration significantly decreased bladder contraction frequency and increased URS-EMG activity to levels similar to previous reports. Cardiorespiratory parameters and blood gas levels remained consistent throughout the experiment. The epithelium of the bladder and urethra were greatly damaged and edema and infiltration of neutrophils in the lamina propria of urethra were observed. These data provide an ample evaluation of the health of the animals, stability of voiding function and appropriateness of the model for testing drugs designed to evaluate lower urinary tract as well as cardiovascular and respiratory systems function.
authors.affiliation: Urogenix Inc./Astellas, Durham, North Carolina, United States of America.
authors.forename: F Aura
authors.initials: FA
authors.lastname: Kullmann
authors.forename: Grace I
authors.initials: GI
authors.lastname: Wells
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Langdale
authors.forename: Jihong
authors.initials: J
authors.lastname: Zheng
authors.forename: Karl B
authors.initials: KB
authors.lastname: Thor
mesh_terms: D019342:Acetic Acid; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000758:Anesthesia / Q000379:methods*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002698:Chloralose / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D000068736:Duloxetine Hydrochloride; D004576:Electromyography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014521:Urethra / Q000187:drug effects / Q000503:physiopathology; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology*; D001745:Urinary Bladder Diseases / Q000139:chemically induced / Q000503:physiopathology*; D014554:Urination / Q000187:drug effects
chemical_list: D018759:Adrenergic Uptake Inhibitors; D006993:Hypnotics and Sedatives; D013876:Thiophenes; D002698:Chloralose; D000068736:Duloxetine Hydrochloride; D019342:Acetic Acid
references.citation: Acta Physiol Scand. 1971 Jan;81(1):47-53
references.pmid: 5543316
references.citation: J Pharmacol Exp Ther. 1995 Aug;274(2):1014-24
references.pmid: 7636716
references.citation: Eur J Pharmacol. 1995 Dec 12;287(2):173-7
references.pmid: 8749032
references.citation: BJU Int. 2009 Feb;103(4):530-6
references.pmid: 19007383
references.citation: Urology. 2003 Oct;62(4 Suppl 1):3-9
references.pmid: 14550831
references.citation: J Physiol. 1994 Sep 15;479 ( Pt 3):451-61
references.pmid: 7837101
references.citation: Eur J Pharmacol. 2012 May 15;683(1-3):252-9
references.pmid: 22421400
references.citation: J Pharmacol Exp Ther. 1998 May;285(2):680-6
references.pmid: 9580613
references.citation: Neurourol Urodyn. 2000;19(1):87-99
references.pmid: 10602250
references.citation: J Physiol. 1979 Sep;294:105-22
references.pmid: 512936
references.citation: Neuroscience. 1989;31(3):807-15
references.pmid: 2480554
references.citation: Am J Physiol Regul Integr Comp Physiol. 2010 May;298(5):R1198-208
references.pmid: 20164207
references.citation: J Urol. 2005 Mar;173(3):1011-5
references.pmid: 15711367
references.citation: J Urol. 2001 Oct;166(4):1539-48
references.pmid: 11547128
references.citation: Neurourol Urodyn. 2012 Jan;31(1):30-5
references.pmid: 22038779
references.citation: Brain Res Dev Brain Res. 1989 Mar 1;46(1):137-44
references.pmid: 2706767
references.citation: Am J Physiol. 1980 Jul;239(1):R137-42
references.pmid: 7396029
references.citation: Q J Exp Physiol Cogn Med Sci. 1965 Jul;50(3):263-70
references.pmid: 5175132
references.citation: Am J Vet Res. 2007 Feb;68(2):203-7
references.pmid: 17269887
references.citation: J Urol. 2009 Jul;182(1):366-73
references.pmid: 19447414
references.citation: Vet Rec. 1972 Sep 30;91(14):330-3
references.pmid: 4562133
references.citation: Am J Physiol. 1999 Oct;277(4):R1002-12
references.pmid: 10516238
references.citation: Neuropharmacology. 1984 Jan;23(1):43-8
references.pmid: 6717753
references.citation: J Auton Nerv Syst. 1990 Jul;30 Suppl:S71-7
references.pmid: 2212495
references.citation: Neurosci Lett. 2012 May 10;516(1):34-8
references.pmid: 22480694
references.citation: J Pharmacol Toxicol Methods. 2008 May-Jun;57(3):188-93
references.pmid: 18367412
references.citation: Br J Pharmacol. 2006 Feb;147 Suppl 2:S25-40
references.pmid: 16465182
references.citation: J Comp Neurol. 1956 Nov;106(1):213-45
references.pmid: 13398495
references.citation: J Neurocytol. 1998 Mar;27(3):141-55
references.pmid: 10640174
references.citation: Am J Physiol Renal Physiol. 2009 Apr;296(4):F892-901
references.pmid: 19158342
references.citation: Am J Physiol Renal Physiol. 2008 Oct;295(4):F1248-53
references.pmid: 18753298
references.citation: J Physiol. 2006 Nov 15;577(Pt 1):115-26
references.pmid: 16945977
references.citation: Life Sci. 2002 Aug 2;71(11):1227-36
references.pmid: 12106588
references.citation: J Auton Nerv Syst. 1997 Sep 10;66(1-2):97-104
references.pmid: 9334999
references.citation: J Physiol. 1965 Aug;179(3):509-17
references.pmid: 5858628
references.citation: J Pharmacol Exp Ther. 1988 Nov;247(2):765-73
references.pmid: 3183970
references.citation: Br J Pharmacol. 2006 May;148(2):154-61
references.pmid: 16547526
references.citation: Am J Vet Res. 2011 Apr;72(4):578-82
references.pmid: 21453161
references.citation: Auton Neurosci. 2010 Feb 16;153(1-2):33-40
references.pmid: 19666243
references.citation: Nat Clin Pract Urol. 2008 Apr;5(4):188-9
references.pmid: 18334974
references.citation: Neuroreport. 1994 Aug 15;5(13):1673-8
references.pmid: 7819545
references.citation: J Clin Invest. 1999 May;103(9):1269-76
references.pmid: 10225970
references.citation: Biol Neonate. 1994;66(6):316-23
references.pmid: 7727613
references.citation: J Physiol. 2011 Dec 1;589(Pt 23):5833-43
references.pmid: 22005674
references.citation: Am J Physiol. 1991 Dec;261(6 Pt 2):R1560-7
references.pmid: 1750580
references.citation: Am J Physiol. 1972 Sep;223(3):660-7
references.pmid: 5055323
references.citation: Am J Physiol Regul Integr Comp Physiol. 2010 Aug;299(2):R416-38
references.pmid: 20484700
references.citation: Br J Pharmacol. 2009 Dec;158(7):1655-62
references.pmid: 19860742
references.citation: J Physiol. 1969 Jan;200(1):87-108
references.pmid: 5248885
references.citation: Am J Physiol. 1988 Sep;255(3 Pt 2):H419-25
references.pmid: 2843054
references.citation: J Urol. 1983 Jan;129(1):202-5
references.pmid: 6681849
references.citation: Brain Res Dev Brain Res. 1990 Dec 15;57(2):255-61
references.pmid: 1705869
references.citation: Nat Rev Neurosci. 2008 Jun;9(6):453-66
references.pmid: 18490916
references.citation: Exp Neurol. 2008 Jul;212(1):218-25
references.pmid: 18502417
references.citation: J Urol. 2011 Jul;186(1):326-30
references.pmid: 21600604
references.citation: Eur J Pharmacol. 1991 Mar 26;195(2):301-4
references.pmid: 1678710
references.citation: J Urol. 2001 Apr;165(4):1294-9
references.pmid: 11257704
references.citation: Scand J Urol Nephrol Suppl. 1996;179:81-5
references.pmid: 8908670