• International Neurourology Journal
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• 제22권4호
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• pp.275-286
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• 2018

Purpose: OnabotulinumtoxinA (BoNT-A) is a promising therapy for treating neurogenic detrusor overactivity (NDO) in individuals with spinal cord injury (SCI). This systematic review and meta-analysis aimed to carry out an in-depth review and to make an objective estimation of the efficacy and safety of BoNT-A on NDO after SCI. Methods: The PubMed, Embase, and Cochrane databases were searched for all relevant articles published from 2001 to 2016 that referred to NDO, SCI, and BoNT-A or botulinum toxin A. All data were recorded in an Excel spreadsheet by 2 individual reviewers. Review Manager version 5.3 was used to carry out the meta-analysis. Results: This analysis included 17 studies involving 1,455 patients. Compared with placebo and baseline, BoNT-A was effective in increasing maximum cystometric capacity, volume at first involuntary detrusor contraction, cystometric bladder capacity (all P<0.00001), compliance (P=0.001), and the number of patients with complete dryness (P=0.0003), and decreasing detrusor pressure, the number of patients with no involuntary detrusor contractions, the maximum flow rate, the incidence of detrusor overactivity (all P<0.00001), and the number of urinary incontinence episodes (P=0.001). There were no statistically significant differences between doses of 200 U and 300 U or between injections into the detrusor and submucosa. There were no life-threatening adverse events. Conclusions: BoNT-A is effective and safe in treating NDO after SCI. There were no statistically significant differences between doses of 200 U and 300 U or between injecting into the detrusor and submucosa. However, more high-quality randomized controlled trials are still needed.

• International Neurourology Journal
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• 제22권4호
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• pp.268-274
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• 2018

Purpose: To describe a technique for urodynamic diagnosis of detrusor sphincter dyssynergia (DSD) using urethral pressure measurements and examine potential associations between urethral pressure and bladder physiology among patients with DSD. Methods: Multiple sclerosis (MS) and spinal cord injured (SCI) patients with known DSD diagnosed on videourodynamics (via electromyography or voiding cystourethrography) were retrospectively identified. Data from SCI and MS patients with detrusor overactivity (DO) without DSD were abstracted as control group. Urodynamics tracings were reviewed and urethral pressure DSD was defined based on comparison of DSD and control groups. Results: Seventy-two patients with DSD were identified. Sixty-two (86%) had >20 cm $H_2O$ urethral pressure amplitude during detrusor contraction. By comparison, 5 of 23 (22%) of control group had amplitude of >20 cm $H_2O$ during episode of DO. Mean duration of urethral pressure DSD episode was 66 seconds (range, 10-500 seconds) and mean urethral pressure amplitude was 73 cm $H_2O$ (range, 1-256 cm $H_2O$). Longer (>30 seconds) DSD episodes were significantly associated with male sex (81% vs. 50%, P=0.013) and higher bladder capacity (389 mL vs. 219 mL, P=0.0004). Urethral pressure amplitude measurements during DSD were not associated with significant urodynamic variables or neurologic pathology. Conclusions: Urethral pressure amplitude of >20 cm $H_2O$ during detrusor contraction occurred in 86% of patients with known DSD. Longer DSD episodes were associated with larger bladder capacity. Further studies exploring the relationship between urethral pressure measurements and bladder physiology could phenotype DSD as a measurable variable rather than a categorical observation.

• The Korean Journal of Physiology and Pharmacology
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• 제3권4호
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• pp.439-445
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• 1999

This study is to investigate the mechanism of inhibitory effect of imipramine on the calcium utilization in single cells isolated from canine detrusor. 2 mm thick smooth muscle chops were incubated in 0.12% collagenase solution at $36^{circ}C,$ and aerated with 95% $O_2/5%\;CO_2,$ and then cell suspension was examined. Acetylcholine (ACh) evoked a concentration-dependent contraction of the isolated detrusor cells in normal physiologic salt solution (PSS), and the ACh-induced contraction was significantly inhibited by imipramine. In $Ca^{2+}-free$ PSS, ACh-induced contraction was less than those in normal PSS and it was not affected by the pretreatment with imipramine. $Ca^{2+}-induced$ contraction in $Ca^{2+}-free$ PSS was supressed by imipramine, but addition of A 23187, a calcium ionophore, overcomed the inhibitory effect of imipramine. High potassium-depolarization (40 mM KCl) evoked cell contraction, which was inhibited by imipramine. Caffeine, a releasing agent of the stored $Ca^{2+}$ from sarcoplasmic reticulum, evoked a contraction of the cells that was not blocked by the pretreatment with imipramine. These results suggest that imipramine inhibits the influx of calcium in the detrusor cells through both the receptor-operated- and voltage-gated-calcium channels, but does not affect the release of calcium from intracellular storage site.

• 한국정밀공학회지
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• 제29권5호
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• pp.584-590
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• 2012

The structural and functional disorder of a detrusor induces a bladder hypertrophy and degenerates a bladder muscle gradually by preventing normal urination. Thus, the thickness of the bladder wall has been increased in proportion to the degree of bladder outlet obstruction. In this study, the mechanical characteristics of the detrusor is analyzed for the physical properties and the thickness changes of the bladder muscle using a mathematically analytic method. In order to obtain the mechanical property of the bladder muscle, the tensile test of porcine bladder tissue is performed because its property is similar to that of human. The result of tensile test is applied to the mathematically model as Mooney Rivlin coefficients which represent the hyperelastic material. The model of the bladder is defined as the spherical shape with the initial volume of 50ml. The principal stress and strain according to the thickness are analyzed. Also, computer simulations for three types of the material property for the model of the bladder are performed based on the fact that the stiffness of the bladder is weakened as the progress of the benign prostatic hyperplasia. As a result, the principal stress is 341kPa at the initial thickness of 2.2mm, and is 249kPa at 6.5mm. As the bladder wall thickness increases, the principal stress decreases. The principal stress and strain decrease as the stiffness of the bladder decreases under the same thinkness.

• The Korean Journal of Physiology and Pharmacology
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• 제15권3호
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• pp.143-147
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• 2011

Defensins, cysteine-rich cationic polypeptides released from neutrophils, are known to have powerful antimicrobial properties. In this study, we sacrificed 30 rats to investigate the effects of ${\alpha}$-defensin 1 on detrusor muscle contractions in isolated rat bladder. From the experiments we found relaxing effects of ${\alpha}$-defensin 1 on the contractions induced by phenylephrine (PE) but not by bethanechol (BCh) in the detrusor smooth muscles. To determine the mechanisms of the effects of ${\alpha}$-defensin 1, the changes of effects on PE-induced contraction by ${\alpha}$-defensin 1 pretreatment were observed after pretreatment of Rho kinase inhibitor (Y-27632), protein kinase C (PKC) inhibitor (Calphostin C), potent activator of PKC (PDBu; phorbol 12,13-dibutyrate), and NF-${\kappa}B$ inhibitors (PDTC; pyrrolidinedithiocarbamate and sulfasalazine). The contractile responses of PE ($10^{-9}{\sim}10^{-4}$ M) were significantly decreased in some concentrations of ${\alpha}$-defensin 1 ($5{\times}10^{-9}$ and $5{\times}10^{-8}$ M). When strips were pretreated with NF-kB inhibitors (PDTC and sulfasalazine; $10^{-7}{\sim}10^{-6}$ M), the relaxing responses by ${\alpha}$-defensin 1 pretreatment were disappeared. The present study demonstrated that ${\alpha}$-defensin 1 has relaxing effects on the contractions of rat detrusor muscles, through NF-${\kappa}B$ pathway. Further studies in vivo are required to clarify whether ${\alpha}$-defensin 1 might be clinically related with bladder dysfunction by inflammation process.

• 대한약리학회지
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• 제31권2호
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• pp.195-206
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• 1995

The study was undertaken to examine the possibility of the involvement of $K^+$ channels in the mechanism of relaxant-action of imipramine on the isolated canine detrusor muscle strips. Canine urinary bladder were isolated, and smooth muscle strips of 15 mm long and 2 mm wide from the mid-portion of anterior wall were made in the Tyrode solution of $0{\sim}4^{\circ}C$. The strips were prepared for isometric myography in Biancani's isolated muscle chamber containing 1 ml of Tyrode solution, which was maintained with pH 7.4 by aeration with $95%\;O_2/5%CO_2\;at\;37^{\circ}C$. RP 52891, a non-specific $K^+$ channel opener, concentration-dependently suppressed the spontaneous phasic contractions of the detrusor strips. Imipramine, a tricyclic antidepressant, also reduced the spontaneous contractions in a concentration-dependent manner. RP 52891 was more potent than imipramine(p<0.05), and Imipramine was more efficient than RP 52891(p<0.05).Procaine, a voltage-dependent $K^+$ channel blocker, glibenclamide, an ATP-dependent $K^+$ channel blocker, and apamin, a calcium-dependent $K^+$ channel blocker antagonized the relaxant effect of RP 52891, but not of imipramine. Imipramine reduced the electric field stimulation (EFS) -induced contractions concentration-dependently. None of the $K^+$ channel blockers employed for this study, procaine, glibenclamide or apamin antagonized the inhibitory action of imipramine on the EFS-induced contraction. These results suggest that in canine detrusor, the $K^+$ channels of the characteristics of voltage-dependent, ATP-dependent and/or calcium-dependent are exist, and the inhibitory action of imipramine on the contractility of the detrusor is independent from the $K^+$ channels.

• Journal of Yeungnam Medical Science
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• 제12권2호
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• pp.246-259
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• 1995

배뇨근의 운동성에 대한 baclofen의 억제작용의 기전을 탐구하기 위하여 다음과 같은 실험을 하였다. 흰쥐 (Sprague-Dawley)의 방광에서 적출한 배뇨근절편을 적출근편실험조에 현수하고, 등척성 장력측정기를 사용하여 그 수축력을 묘기하였다. 실험조내의 영양액의 온도는 $37^{\circ}C$로 유지시키고, 95% 산소와 5% 이산화탄소의 혼합기체를 공급하여 pH를 7.4로 유지하였다. 배뇨근절편은 전기장자극에 의해 수축하였는데, 8분간의 전기장자극 유발수축 중 최초의 급격한 수축반응은 mATP와 baclofen에 의해 약간 억제되는 경향을 보였으며, 후기 4분간의 수축반응은 콜린성 무스카린성 수용체 봉쇄제인 atropine과 $GABA_B$ 수용체 효현제인 baclofen에 의해 유의하게 억제되었다. Atropine은 배뇨근 절편의 acetylcholine 유발 수축을 길항하였고, mATP는 ATP 유발 수축을 완전히 봉쇄하였으나, baclofen 존재하에서는 acetylcholine이나 ATP 첨가에 의한 배뇨근의 수축이 영향을 받지 않았다. 이상의 결과를 종합하면, 흰쥐 방광에는 $GABA_B$ 수용체가 존재하며 baclofen은 이 수용체를 통하여 콜린성신경 말단에서의 신경전달체의 유리를 억제하여 배뇨근의 수축성을 감소시킨다고 사료된다.

• Journal of Yeungnam Medical Science
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• 제11권2호
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• pp.363-374
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• 1994

흰쥐의 적출 배뇨근에 대한 수종의 potassium 통로개방제의 작용을 관찰하고, 배뇨근에 존재하는 potassium 통로의 특성을 알아보기 위하여 체중 250~350g의 흰쥐 (Sprague-Dawley)를 단두하여 희생시킨 후 방광을 적출하였다. 적출된 방광으로 부터 $1.5mm{\times}1.5cm$의 배뇨근 수평절편을 만들어 1ml의 Tyrode 영양액을 포함하는 적출근편실험조에 현수하고 등척성장력을 측정하여 polygraph에 묘기하였다. 배뇨근절편은 potassium 통로 개방제인 pinacidil, BRL 38227 및 RP 52891의 누적 농도 첨가에 의하여 그 기본장력이 농도의존적으로 감소하였는데 그 작용강도는 RP 52891, pinacidil 그리고 BRL 38227의 순이었다. 전위 의존성 potassium 통로 봉쇄제인 procaine은 배뇨근 절편의 기본장력에 영향을 미치지 못했으며, pinacidil, BRL 38227 및 RP 52891에 의한 기본장력감소작용에 대해서도 영향을 미치지 못하였다. 칼슘 의존성 potassium 통로봉쇄제인 apamin은 배뇨근의 기본장력에 유의한 변화를 가져오지 못하였고, potassium 통로 개방제들에 대하여는 상경적 길항작용을 나타내지는 않았으나 BRL 38227과 RP 52891의 최고효능을 유의하게 감소시켰다. ATP 의존성 potassium 통로봉쇄제인 glibenclamide는 배뇨근 절편의 기본장력을 증가시키고, pinacidil을 상경적으로 길항하였으며, BRL 38227과 RP 52891을 상경적으로 길항하는 동시에 그 최대효능을 감소시켰다. 췌장의 ${\beta}$-세포에서 ATP 의존성 potassium 통로를 개방시켜 인슐린의 분비를 억제하는 galanin은 흰쥐의 배뇨근을 수축시켰다. 이상의 결과를 종합하면, 흰쥐의 배뇨근에서는 새로운 potassium 통로 개방제인 RP 52891의 배뇨근 이완작용이 pinacidil보다 강한 것으로 관찰되었다. 또 흰쥐 배뇨근에서는 ATP 의존성이며, glibenclamide 반응성인 potassium 통로가 존재 한다고 생각되는데, 이는 췌장의 ${\beta}$-세포에 있는 ATP 의존성 potassium 통로와는 다른 특성을 가진 것으로 추측된다.

• Journal of Yeungnam Medical Science
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• 제8권2호
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• pp.138-149
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• 1991

흰쥐(Sprague-Dawley)의 방광에서 적출한 배뇨근절편을 적출 근편 실험조에 현수하고, 등척성 장력 측정기를 사용하여 그 수축력을 묘기하였다. 배뇨근 절편은 전기장자극에 의해 수축하였으며, 이 수축반응은 콜린에스테라제 억제약물인 physostigmine에 의해 증가하였고 신경말단에서의 choline 재흡수를 방해하는 hemicholinium에 의해 억제되었으며, 신경절봉쇄약물인 hexamethonium에 의해서는 영향을 받지 않았으나 신경축색전도 억제제인 tetrodotoxin에 의해서 소실되었다. 이러한 전기장자극유발 수축은 콜린성 무스카린성 수용체봉쇄약물인 atropine에 의해 부분적으로 길항되었으며, atropine에 의해 길항되지 않는 부분은 ATP 탈감작에 의해 완전히 소실되었다. 배뇨근 절편은 콜린성 무스카린성 수용체 흥분제인 bethanechol과 퓨린성 수용체 흥분제인 ATP에 의하여 농도의존적 수축력 증가를 나타내었으며, 이중 bethanechol 유발수축은 ATP 탈감작에 의해 영향을 받지 않았고, ATP 유발수축은 tetrodotoxin에 의하여 영향을 받지 않았다. 이상의 결과로 보아 흰쥐의 적출배뇨근에는 흥분성 신경전달체계로서 퓨린성 수용체와 콜린성 수용체가 존재하며, 이들은 서로 영향을 미침이 없이 독자적으로 배뇨근 수축에 기여하고 있다고 사료된다.

• The Korean Journal of Physiology
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• 제26권2호
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• pp.137-141
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• 1992

The present study was aimed at elucidating the mode of inhibitory action of tricyclic antidepressants on the smooth muscle. Effects of amitriptyline on the isolated detrusor muscle strips of the urinary bladder of the rabbit were examined. The spontaneous rhythmic movement of the muscle preparation was frequently observed, which was decreased or abolished by addition of amitriptyline $(10^{-5}{\sim}10^{-3}\;M)$. The muscle preparation responded with contraction dose dependently to carbachol, of which dose response curve shifted to the right in the presence of either amitriptyline or atropine. However, amitriptyline produced a nonparallel shift, whereas atropine caused a parallel one. In calcium free medium, the contraction response to carbachol was markedly decreased, which was resumed by the addition of $CaCl_2$ (2.5mM), but not in the presence of either amitriptyline or nifedipine. KCI (60 mM) produced a potent contraction, which was abolished in the presence of amitriptyline or nifedipine. These results suggest that amitriptyline, unlike atropine, not only acts as a noncompetitive antagonist at cholinergic muscarine receptors but also inhibits Ca-influx through the muscle cell membrane.