Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Neurogastroenterol Motil. 2018 Oct;30(10):e13383. doi: 10.1111/nmo.13383. Epub 2018 Jun 1.
In order to understand the pathophysiology of rectal sensorimotor dysfunctions in women with fecal incontinence (FI) and rectal urgency, we evaluated the effects of a muscarinic antagonist and an adrenergic α agonist on these parameters.
Firstly, rectal distensibility and sensation were evaluated with a barostat and sinusoidal oscillation at baseline and after randomization to intravenous saline or atropine in 16 healthy controls and 44 FI patients. Thereafter, FI patients were randomized to placebo or clonidine for 4 wk; rectal compliance and sensation were revaluated thereafter. The effect of atropine and clonidine on rectal functions and the relationship between them were evaluated.
At baseline, compared to controls, rectal capacity was lower (P = .03) while the mean pressure (P = .02) and elastance (P = .01) during sinusoidal oscillation were greater, signifying reduced distensibility, in FI. Compared to placebo, atropine increased (P ≤ .02) the heart rate in controls and FI and reduced (P = .03) the variability in rectal pressures during sinusoidal oscillation in controls. Clonidine increased rectal compliance (P = .04) and reduced rectal capacity (P = .03) in FI. The effects of atropine and clonidine on compliance (r = .44, P = .003), capacity (r = .34, P = .02), pressures during sinusoidal oscillation (r = .3, P = .057), pressure (r = .6, P < .0001), and volume sensory thresholds (r = .48, P = .003) were correlated.
The effects of atropine and clonidine on rectal distensibility and sensation were significantly correlated. A preserved response to atropine suggests that reduced rectal distensibility is partly reversible, mediated by cholinergic mechanisms, and may predict the response to clonidine, providing a pharmacological challenge.
为了了解女性粪便失禁和直肠急迫感患者直肠感觉运动功能障碍的病理生理学,我们评估了毒蕈碱拮抗剂和肾上腺素能 α 激动剂对这些参数的影响。
首先,我们使用测压计和正弦振荡器在基线和随机静脉注射生理盐水或阿托品后评估 16 名健康对照者和 44 名粪便失禁患者的直肠可扩张性和感觉。此后,粪便失禁患者被随机分配接受安慰剂或可乐定治疗 4 周;此后重新评估直肠顺应性和感觉。评估了阿托品和可乐定对直肠功能的影响及其相互关系。
与对照组相比,基线时粪便失禁患者的直肠容量较低(P=0.03),而正弦振荡器期间的平均压力(P=0.02)和弹性(P=0.01)较大,提示直肠扩张性降低。与安慰剂相比,阿托品增加了对照组和粪便失禁患者的心率(P≤0.02),并降低了对照组正弦振荡器期间直肠压力的变异性(P=0.03)。可乐定增加了粪便失禁患者的直肠顺应性(P=0.04),降低了直肠容量(P=0.03)。阿托品和可乐定对顺应性(r=0.44,P=0.003)、容量(r=0.34,P=0.02)、正弦振荡器期间的压力(r=0.3,P=0.057)、压力(r=0.6,P<0.0001)和容积感觉阈值(r=0.48,P=0.003)的影响呈正相关。
阿托品和可乐定对直肠可扩张性和感觉的影响具有显著相关性。对阿托品反应良好表明,直肠可扩张性降低部分是可逆的,由胆碱能机制介导,并且可能预测可乐定的反应,提供药理学挑战。