Pharyngoesophageal and cardiorespiratory interactions: potential implications for premature infants at risk of clinically significant cardiorespiratory events

Abstract

The aims of this study were to 1) examine pharyngoesophageal and cardiorespiratory responses to provoking pharyngeal stimuli, and 2) to determine potential contributory factors impacting heart rate (HR) changes to provide insight into cardiorespiratory events occurring in preterm infants. Forty-eight neonates (19 females and 29 males, born at 27.7 ± 0.5 wk; mean ± SE) pending discharge on full oral feeds were studied at 38.7 ± 0.2 wk postmenstrual age using concurrent pharyngoesophageal manometry, electrocardiography, respiratory inductance plethysmography, and nasal airflow thermistor. Pharyngoesophageal and cardiorespiratory responses (prevalence, latency, and duration) were quantified upon abrupt pharyngeal water stimuli (0.1, 0.3, and 0.5 ml in triplicate). Mixed linear models and generalized estimating equations were used for comparisons between HR changes. Contributory factors included stimulus characteristics and subject characteristics. Of 338 pharyngeal stimuli administered, HR increased in 23 (7%), decreased in 108 (32%), and remained stable in 207 (61%) neonates. HR decrease resulted in repetitive swallowing, increased respiratory-rhythm disturbance, and decreased esophageal propagation rates (all, P < 0.05). HR responses were related to stimulus volume, stimulus flow rate, and extreme prematurity (all, P < 0.05). In preterm infants, HR remains stable in a majority of pharyngeal provocations. HR decrease, due to pharyngeal stimulation, is related to aberrant pharyngoesophageal motility and respiratory dysregulation and is magnified by prematurity. We infer that the observed aberrant responses across digestive, respiratory, and cardiovascular systems are related to maladaptive maturation of the parasympathetic nervous system. These aberrant responses may provide diagnostic clues for risk stratification of infants with troublesome cardiorespiratory events and swallowing difficulty. NEW & NOTEWORTHY Cardiorespiratory rhythms concurrent with pharyngeal, upper esophageal sphincter, and esophageal body responses were examined upon pharyngeal provocation in preterm-born infants who were studied at full-term maturation. Decreased heart rate (HR) was associated with extreme preterm birth and stimulus flow/volume. With HR decrease responses, aerodigestive reflex abnormalities were present, characterized by prolonged respiratory rhythm disturbance, repetitive multiple swallowing, and poor esophageal propagation. Promoting esophageal peristalsis may be a potential therapeutic target.

Keywords: cardiorespiratory rhythms; esophageal motility; life-threatening events; prematurity; swallowing.

Fig. 1.

Evaluation of cardiac responses to pharyngeal stimuli. Depicted is a representative tracing of concurrent pharyngoesophageal motility and cardiorespiratory responses to pharyngeal stimuli (0.5 ml). Potential responses included no heart rate (HR) change (A), HR increase (B), or HR decrease (C). HR change was defined as 10% change from baseline (indicated by the gray dashed lines). HR response latency was defined as the time between stimulus onset (black vertical line) and 10% HR change. HR response duration was defined as the time between 10% change onset to 10% change offset. Note with the HR increase response, the R-R interval decreases, indicating increased sympathetic tone. Conversely, with the HR decrease response, the R-R interval increases, indicating increased parasympathetic tone.

Fig. 2.

Effects of pharyngeal stimulus volume on HR. *P < 0.05 for comparison. A: HR response frequency is given as a percentage. The HR increase or decrease is increased with the higher stimulus volumes (0.3 and 0.5 ml). If a HR response occurs, HR decrease is more frequent. B: actual HR (in beats per minute) also significantly differs with HR response, with HR decrease greater in magnitude.

Fig. 3.

Diagrammatic representation of sequential timing of pharyngoesophageal and cardiorespiratory responses to pharyngeal stimuli. The figure was adapted from response latency and response duration values in Table 2. Along the x-axis is elapsed time with 0 s representing pharyngeal stimulus onset. *P < 0.05 for HR response onset. †P < 0.05 for HR response duration. Note that although respiratory, pharyngeal, and esophageal response timings were similar, the cardiac response is distinct between HR increase and HR decrease for both response onset and duration. Also note for HR decrease, cardiac response latency occurs after respiratory rhythm change and pharyngeal swallowing, but before esophageal peristalsis.