The primary function of the esophagus is to transport swallowed material from the pharynx to the stomach. Although immature pharyngeal function has long been a great concern in neonatology, abnormal esophageal motility has recently been recognized in numerous neonatal conditions, including gastroesophageal reflux disease (GERD) (1), premature birth (2,3), and esophageal atresia (4). Treatments proposed to improve swallowing disorders include modification of ingesta volume, composition or viscosity (5,6), and manipulation of bolus temperature (7). The latter stems from the recognition that temperature-sensitive transient receptor potential (TRP) channels in the oropharynx, such as TRPV1 and TRPM8, can improve the swallowing reflex. Identical TRP channels have been described in the esophagus and a few studies have shown the effects of varying food temperature on esophageal motility in adult humans (8,9); however, to our knowledge, no data are available in newborns.
Previous in vivo studies have demonstrated similarities between the ovine and human esophagus with respect to thickness and histological structure (10). This led us to hypothesize that the lamb is a relevant model for swallowing studies in certain neonatal conditions.
Our aim was thus to determine esophageal motility characteristics under different milk temperature conditions in the healthy, newborn lamb at term, using multichannel intraluminal impedance-pH monitoring (MII-pH).
The 5 lambs involved in the study were born at term by spontaneous vaginal delivery. They were ages 2 to 3 days and weighed 3.6(0.7) kg on the experimental day. They were also included in another study aiming at describing a new model of neonatal gastroesophageal reflux. The nonsedated lambs underwent a 24-hour esophageal MII-pH (MMS, Enschede, the Netherlands), during which they moved freely in a plexiglas chamber and could bottle-feed with reconstituted ewe milk ad libitum. The chamber was placed in a temperature-controlled room, which was held at an ambient temperature of 26°C. The 2-mm diameter MII-pH catheter (Unisensor, Attikon, Switzerland) has a pH-measuring electrode positioned at 2 cm from the probe's distal tip and 7 impedance sensors. Following calibration, the catheter was introduced into the esophagus via the nose by pulling it through a 10-F suction catheter, to prevent coiling of the catheter in the nasopharynx. The probe was anchored to the head skin with 2 stitches. Correct positioning of the catheter (pH electrode 3 cm above the cardioesophageal junction) was confirmed by x-ray and verified at necropsy. The signals from the impedance and pH channels were sampled at 50 and 8 Hz, respectively, stored in the battery-powered data logger, and downloaded into a personal computer. MII-pH recordings were analyzed with Database Software (version 8.9a; MMS) and visually verified.
For the present study, lambs were comfortably positioned in a sling at the end of the 24-hour MII-pH monitoring. They were given a 50-mL bottle of reconstituted ewe milk at 3 different temperatures in random order: 26°C (ambient temperature), 38.5°C (within the normal range of lamb's body temperature 38–40°C), and 41.5°C (above the maximum value of lamb's body temperature). The milk was warmed in a digital water bath that provides a reliable temperature control (temperature uniformity ±0.2°C and stability ±0.25°C). When the desired temperature was reached, the milk was given immediately. The suckling duration was <15 seconds. The same custom-designed bottle and teat were used for all lambs. Two successive feeding episodes were separated by 1 hour. The study was approved by the ethics committee for animal care and experimentation of the Université de Sherbrooke, Québec.
Definitions of swallowing variables and features of a bolus swallow using MII-pH have been described previously (4). Bolus entry at a specific level was measured at the 50% point between preswallow impedance baseline and lowest impedance point during bolus presence. Bolus exit was determined as the return to this 50% point on the impedance recovery curve. Esophageal swallowing was evaluated by manual assessment of the following specific motility parameters:
- Bolus presence time (BPT): time elapsed between bolus entry and bolus exit at each impedance-measuring site.
- Total bolus transit time (TBTT): time elapsed between bolus entry at the most proximal recording segment and bolus exit at the most distal recording segment.
- Segmental transit time (STT): time elapsed between bolus entry at a given level above lower esophageal sphincter (LES) and bolus exit at the next lower level.
- Total propagation velocity: speed with which the bolus crosses all of the impedance channels.
- Bolus head advance time (BHAT): time elapsed between bolus entry at 20 cm above LES and bolus entry at 15, 10, and 5 cm above LES.
Swallows were classified by MII as complete bolus transit if bolus entry occurred at the most proximal site and bolus exit points were recorded in all distal impedance-measuring sites or incomplete bolus transit if bolus exit was not identified at any of the distal impedance-measuring sites.
Statistical analyses were performed using Prism software version 5.04 (GraphPad Software, San Diego, CA). Data are presented as mean (SD). The Friedman test was used to compare data for the 3 milk temperatures, followed by a Dunn post-hoc test as appropriate.
Mean lamb body temperature was 39.1°C (0.9). All swallowing variables were successfully studied at each temperature (Table 1). Temperature had no effect on swallow number (26°C: 34 ; 38.5°C: 33 ; 41.5°C: 34 , P > 0.1) and mean bolus volume (26°C: 1.4 mL [1.2]; 38.5°C: 1.5 mL ; 41.5°C: 1.4 mL [0.8], P > 0.1). Although no temperature effects were observed for BPT at any segment (P > 0.1), the mean TBTT was significantly shorter at 38.5°C (P < 0.05) compared with 26°C and 41.5°C. Moreover, the total propagation velocity was significantly higher at 38.5°C (P < 0.05) compared with 26°C and 41.5°C, whereas the mean STT and STT for segments Z4–Z5 and Z5–Z6 tended to be increased at 39.5°C compared with 26°C and 41.5°C (P < 0.1). Finally, there were no temperature effects on BHAT at any distance above LES (P > 0.1).
The overall message from our results is that bolus propagation velocity in the esophagus is maximal when ewe milk is ingested from a bottle at body temperature in lambs.
Few data are available on esophageal thermoreceptors and their effect on esophageal motility. Three types of thermoreceptors have been described in cats, such as warm (range of discharge 39°C–50°C), cold (10°C–35°C), and mixed receptors (10°C–35°C and 39°C–50°C). Although warm receptor stimulation depresses nerve-induced contractions of the proximal esophagus, cold receptor stimulation increases them (11). In adult humans, although some studies concluded that ice-cold (0°C–4°C) water increases mean esophageal transit time and hot water (60°C) has the opposite effects, a later study did not find any effects of temperature (1°C–60°C) (9). Our results in lambs suggest that modulation of esophageal thermoreceptor activity by milk temperature can alter esophageal body motility in newborn mammals.
Transposition of the present results from lambs to human infants, wherein bolus propagation velocity is 5 to 10 times slower, suggests clinical significance in newborns. Importance of the present results relates, thus, to the immature esophageal motility of the newborn, especially preterm (2,3), as well as anomalies of this motility in disorders such as GERD (1), diaphragmatic hernia (12), gastroschisis (13), or esophageal atresia (4). We propose that studies in human newborns should be performed to test the hypothesis that the esophageal phase of swallowing can be improved by using milk temperature close to body temperature in conditions with immature or impaired esophageal motility.
The authors gratefully acknowledge the MMS Company (Enschede, The Netherlands) for the gracious loan of the MII-pH monitoring equipment.
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