Effect of nifedipine on anorectal sensorimotor functions in health and fecal incontinence

Abstract

The mechanisms of increased rectal stiffness in women with fecal incontinence (FI) and rectal urgency are not understood. Our hypothesis was that distention-induced activation of mechanosensitive L-type calcium channels in smooth muscle contributes to increased rectal stiffness in FI. Anal pressures, rectal distensibility (compliance, capacity, and contractile response to sinusoidal oscillation), and rectal sensation were assessed before and after oral nifedipine (30 + 10 mg) or placebo in 16 women with FI and 16 asymptomatic women. At baseline, FI patients had a lower anal pressure increment during squeeze (health, 66.9 ± 7.6: FI, 28.6 ± 5.9, mean ± SE, P ≤ 0.01), lower rectal capacity (P = 0.052), and higher rectal pressures during sinusoidal oscillation (health, 13.7 ± 3.2: FI, 21.7 ± 1.4, mean ± SE, P = 0.02) than the healthy women, which suggests an exaggerated rectal contractile response to distention. Nifedipine decreased mean BP, increased heart rate (P = 0.01 vs. placebo), and reduced anal resting pressure (P ≤ 0.01) but did not significantly modify rectal distensibility in health or FI. Plasma nifedipine concentrations (health, 103 ± 21 ng/ml: FI, 162 ± 34 ng/ml) were correlated with increased rectal compliance (r = 0.6, P = 0.02) in all study participants and, in healthy subjects, with decreased rectal pressures during sinusoidal oscillation (r = 0.86, P = 0.01), indicative of reduced stiffness. No consistent effects on rectal perception were observed. These observations confirm that FI is associated with anal weakness and increased rectal stiffness. At therapeutic plasma concentrations, nifedipine reduced anal resting pressure but did not improve rectal distensibility in FI, outcomes that argue against a predominant contribution of myogenic L-type calcium channels to reduced rectal distensibility in FI.

Fig. 1.

Study design. Anal manometry, rectal pressure-volume relationships with a barostat, and sinusoidal oscillation were assessed before and after nifedipine (2 doses, 30 and 10 mg orally) or placebo. Plasma nifedipine concentrations were assessed two times.

Fig. 2.

Balloon pressure waveform during sinusoidal oscillation (25 ml) at 5 counts/min in a healthy subject (2 panels on top) and a patient with fecal incontinence (FI) (2 panels on bottom). Data were acquired and depicted at 10 Hz. While sinusoidal oscillation was performed for 20 min, data for the first 10 min are shown for clarity. For simplicity, pre- and postdrug volumetric oscillations are superimposed. Rectal pressures during sinusoidal oscillation before drug were substantially higher in the FI patient than the healthy subject. While rectal pressures were comparable before and after placebo in the healthy subject, nifedipine reduced rectal pressure and its variability in the FI patient.

Fig. 3.

Effects of nifedipine and placebo on mean pressures (top) and pressure variability (bottom) in health and FI. Data are averaged across sinusoidal oscillation epoch at 5 counts/min for 20 min. *P = 0.02 for FI vs. health (pooled baseline). †P = 0.051 for FI vs. health (pooled baseline).