Researchers from the Department of Pediatrics at Case Western Reserve University School of Medicine and University Hospitals Rainbow Babies and Children’s Hospital presented; results of a study that investigated whether there are any deleterious effects of prostaglandin E1 (PGE1); treatment on breathing and whether these effects would be prevented via pre-treatment with caffeine.

Congenital heart disease

The study, called “Caffeine prevents prostaglandin E1-induced disturbances in respiratory neural control: therapeutic implications for infants treated for congenital heart disease,” presented as a platform discussion at the 2019 Pediatric Academic Societies Meeting in Baltimore. Following a single injection of PGE1, whole-body plethysmography was used in baby rats to assess their ability to increase breathing (called the hypoxic ventilatory response, HVR) in response to an acute hypoxic challenge.

Therefore in subsets of animals, rats received a subcutaneous injection of caffeine (5mg/kg, which has been shown to an antagonist of adenosine receptors in the brain); one hour prior to PGE1. Brainstem regions containing respiratory control centers removed and tested via RT-PCR for markers of inflammation (TNFα, IL-1β, IL-6, and iNOS); microglia (Iba-1). So two hours after PGE1 injection; the rats exhibited a significant alteration in the HVR; a finding suggestive of unstable breathing possibly via an undesirable disruption of CNS respiratory neural control regions.

The mRNA expression

Further supportive evidence of a CNS effect of PGE1 on breathing was the finding that PGE1; but also decreased brainstem Iba-1 (a marker of microglia) mRNA expression. Microglia are the resident immune cells of the CNS and have previously shown to modulate breathing; but this study is the first to show that they may play a role in mediating the respiratory disturbances associated with PGE1. Perhaps the most surprising finding was that pretreatment with caffeine prevented all the adverse effects of PGE1; on both breathing and Iba-1 expression. A more selective adenosine 2A receptor antagonist (MSX-3); had a similar beneficial effect.
Their conclusions: “They propose that PGE exerts adenosine-mediated effects on brainstem mechanisms of respiratory control; which may lead to destabilization of breathing in human infants undergoing treatment for congenital heart disease. Prostaglandin’s effects could ediated through microglia; caffeine could be a convenient treatment to prevent respiratory instability in infants receiving PGE1 infusion.”