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Neurodevelopmental Reflex Testing in Neonatal Rat Pups
Published on: April 24, 2017
Caffeine impairs gastrointestinal function in newborn rats
Christopher Welsh1, Jingyi Pan1, Jaques Belik2
1Physiology & Experimental Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Insights
Caffeine impairs gastrointestinal function in newborn rats by relaxing muscles and slowing gastric emptying. This finding suggests caffeine may contribute to feeding intolerance in premature infants, warranting further clinical study.
Area of Science:
- Neonatal Physiology
- Pharmacology
- Gastroenterology
Background:
- Feeding intolerance is common in premature infants.
- Caffeine treats apnea of prematurity but its effect on neonatal gastrointestinal function is unknown.
- Caffeine is known to reduce lower esophageal sphincter (LES) muscle tone.
Purpose of the Study:
- To investigate the effect of caffeine on esophageal and gastrointestinal motor function in newborn rats.
- To determine caffeine's impact on tissue mechanical properties and in vivo gastric emptying rate.
Main Methods:
- Assessed caffeine's effects on LES, gastric, ileal, and colonic muscle force and relaxation in newborn and adult rats.
- Evaluated caffeine-induced changes in newborn gastric emptying rate after fasting.
Main Results:
- Caffeine relaxed precontracted LES and fundal muscle, reduced gastric and intestinal muscle contraction, and delayed gastric emptying in pups.
- The muscle relaxant effect of caffeine was age-independent and ryanodine receptor-mediated.
Conclusions:
- Caffeine impairs LES and gastrointestinal motor function in newborn rats at therapeutic doses.
- Clinical investigation is needed to explore caffeine's contribution to neonatal feeding intolerance.
Background:
Feeding intolerance is commonly documented in premature infants. Caffeine is routinely utilized for apnea of prematurity treatment and known to reduce the lower esophageal sphincter (LES) muscle tone, but the caffeine effect on the newborn gastrointestinal function is unknown. We hypothesized that caffeine impairs esophageal and gastrointestinal motor function. As such, we investigated the drug effect on the tissue's mechanical properties and the newborn rat's in vivo gastric emptying rate.
Methods:
The effects of caffeine on LES, gastric fundal and antrum, as well as ileal and colonic muscle force potential and relaxation response, were measured in newborn and adult rats. The caffeine-induced (10 mg/kg i.p.) newborn gastric emptying rate changes were evaluated following 3 h of fasting.
Results:
Caffeine relaxed the precontracted LES and fundal muscle (P < 0.01), reduced the gastric and intestinal muscle contraction (P < 0.01), and delayed the pups' gastric emptying time (P < 0.01). The caffeine-induced muscle relaxant effect was independent of age and mediated via ryanodine receptors.
Conclusion:
Caffeine administration to newborn rats at a dose comparable to the one therapeutically used for preterm neonates impairs LES and gastrointestinal motor function. Further clinical investigation on the possible contribution of caffeine to neonatal feeding intolerance is warranted.
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