Mechanisms of Meconium Passage: Cholinergic Stimulation of Electromechanical Coordination in the Fetal Colon

Abstract

Objective: Fetal gastrointestinal function develops in utero, with evidence of enhanced motility near-term. Although colonic passage of meconium in utero may be associated with fetal maturation or stress, little is known of the mechanisms potentiating motility. We assessed the effect of bethanechol, a cholinergic prokinetic agent, on colonic muscle muscular contractile and electromyogram (EMG) activity in the near-term ovine fetus.

Methods: Near-term (130 days, n = 8) singleton ovine fetuses were chronically prepared with vascular catheters and three sets of miniature strain gauges and bipolar EMGs on the serosal surface of the transverse colon, left colic flexure, and distal colon. Following a 60-minute control period, fetuses received intravenous bethanechol (60 μg/kg, Low-Beth; 120 μg/kg, High-Beth) at 60 and 180 minutes. Colonic activity was recorded digitally and analyzed for short-duration (2<SHORT< 15 seconds) and long-duration (15<LONG< 120 seconds) strain gauge and EMG contractions. Data were expressed as means ± SEM and analyzed using one-way analysis of variance (ANOVA) and paired t test.

Results: During the control period, there was significantly greater SHORT versus LONG strain gauge contractions in all segments (P <. 05). As compared to control values, Low-Beth and High-Beth signficantly increased SHORT strain gauge contractions in the transverse colon (160 ± 13 to 201 ± 36 and 307 ± 74 spikes/30 min, respectively, P <.05), although not in left colic flexure or distal colon. Bethanecol did not affect LONG strain gauge contractions. SHORT-EMG and LONG-EMG spike bursts did not change in response to bethanecol (280 ± 20, 59 ± 2 spikes/30 min, respectively).

Conclusion: Cholinergic stimulation of fetal sheep colonic activity at 0.9 gestation occurs in the transverse colon, but not the more distal left colic flexure or distal colon. The increased strain gauge, but not EMG activity, suggests that cholinergic stimulation improves electromechanical coordination in the fetal colon. We speculate that cholinergic-induced delivery of gastrointestinal contents to the distal colon evokes local contractile/expulsive mechanisms resulting in meconium passage.