Intravesical protamine sulfate and potassium chloride as a model for bladder hyperactivity

Intravesical protamine sulfate and potassium chloride as a model for bladder hyperactivity
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DOI:
10.1016/s0090-4295(02)02280-x
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发表时间:
2003-03-01
期刊:
影响因子:
2.1
通讯作者:
Fraser, MO
Fraser, MO
中科院分区:
医学4区
文献类型:
--
作者:
Chuang, YC;Chancellor, MB;Fraser, MO

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目标.采用膀胱内灌注硫酸鱼精蛋白(PS)和生理浓度的氯化钾(KCl)建立大鼠急性膀胱过度活动症动物模型。通过用生理盐水填充膀胱(0.04 mL/min),然后膀胱内输注由KCl(100或500 mM)或PS(10或30 mg/mL)组成的供试品溶液60分钟,在麻醉的雌性大鼠中进行连续膀胱测压(CMG)。随后,向10 mg/mL PS处理动物膀胱内输注100、300或500 mM KCl。部分动物在实验前4天皮下注射辣椒素(125 mg/kg)。与单独KCl(100或500 mM)或低浓度PS(10 mg/mL)不同,膀胱内给予高浓度PS(30 mg/mL)产生刺激作用,收缩间期缩短(80.6%)。输注低浓度PS后,输注300或500 mM KCl产生刺激作用(收缩间期分别减少76.9%或82.9%)。与300 mM KCl(20 - 30分钟)相比,500 mM KCl(10 - 15分钟)后刺激发作更快。辣椒素预处理延迟了刺激效应的发作(约60分钟),并降低了刺激效应的幅度(收缩间期减少了35.5%)。PS治疗后膀胱内注射KCl可激活辣椒素敏感性传入神经和逼尿肌,并可能激活辣椒素抗性传入神经。对尿路上皮屏障功能的适度、非细胞毒性冒犯可导致剧烈的刺激反应。该模型可用于膀胱刺激和多动的研究。(C)2003年,Elsevier Science Inc.
Objectives. An acute animal model for hyperactive bladder in rats was developed using intravesical infusion of protamine sulfate (PS), an agent thought to break down urothelial barrier function, and physiologic concentrations of potassium chloride (KCl).Methods. Continuous cystometrograms (CMGs) were performed in urethane-anesthetized female rats by filling the bladder (0.04 mL/min) with normal saline followed by intravesical infusion of a test solution consisting of either KCl (100 or 500 mM) or PS (10 or 30 mg/mL) for 60 minutes. Subsequently, the 10 mg/mL PS-treated animals were infused intravesically with 100, 300, or 500 mM KCl. Some animals were pretreated with capsaicin (125 mg/kg subcutaneously) 4 days before the experiments.Results. Unlike KCl (100 or 500 mM) or a low concentration of PS (10 mg/mL) alone, the intravesical administration of a high concentration of PS (30 mg/mL) produced irritative effects with a decreased intercontraction interval (by 80.6%). After infusion of a low concentration of PS, infusion of 300 or 500 mM KCl produced irritative effects (intercontraction interval decreased by 76.9% or 82.9%, respectively). The onset of irritation occurred more rapidly after 500 mM KCl (10 to 15 minutes) than after 300 mM KCl (20 to 30 minutes). Capsaicin pretreatment delayed the onset (approximately 60 minutes) and reduced the magnitude (intercontraction interval decreased by 35.5%) of irritative effects.Conclusions. Intravesical administration of KCl after PS treatment activates capsaicin-sensitive afferents and detrusor muscle and presumably capsaicin-resistant afferents, Modest, noncytotoxic affronts to urothelial barrier function can result in dramatic irritative responses. This model may be useful in the study of bladder irritation and hyperactivity. (C) 2003, Elsevier Science Inc.