Brains Breathe: Dopamine's Role In Preterm Infants

Time to add another bullet point to the already impressive list of dopamine's functions in humans. (Poor undergrads who will have yet another line to memorize!) A 2009 paper published in the journal Intensive Care Medicine reports that dopamine, widely used to maintain blood pressure in very preterm infants, facilitates flow-metabolism coupling in preterm brain. In other words, dopamine apparently aids in keeping preterm infants' cerebral oxygen demands in touch with cerebral blood flow.

The study investigated the relationship between cerebral perfusion and oxygen metabolism in preterm infants treated with dopamine because of hypotension with controls having normal blood pressures. And it presents very striking evidence that flow-metabolism coupling in the very preterm brain differs spectacularly from that in the mature brain and the immature brain when dopamine has been used.

Flow-metabolism coupling is a feature of the mature brain. The mechanism sustains cerebral oxygen delivery when cerebral metabolic demand (and thus cerebral oxygen demand) varies. In order to do so, cerebral blood flow increases or decreases accordingly by vasoconstriction or vasodilatation of the cerebral vasculature. It is dopamine which is thought to control the cerebral vasculature's tone. Flow-metabolism is important as it makes sure that the brain is provided with adequate amounts of oxygen: too little would mean hypoxia while too much is of concern because of the putative role of reactive oxygen species in preterm brain injury.

Twenty six very preterm infants (born at <28 weeks gestation) were observed as subjects in the prospective observational study. Ten of the preterm infants were started on dopamine medication by the attending pediatrician (DOPA group) and monitored while the other 16 infants were monitored as controls.

The study showed that in the controls, cerebral metabolic rate of oxygen consumption did not correlate with cerebral blood flow-that is, the amount of cerebral oxygen required was not obtained thanks to less or more blood entering the brain. The results of the DOPA group showed a "head down, legs up" difference: cerebral metabolic rate of oxygen consumption correlates with cerebral blood flow-which is just like in a mature brain! Hence the conclusion that dopamine promotes flow-metabolism coupling in the preterm brain.

While in the mature brain and as it now turns out, the immature brain of the dopamine-treated preterm infant, the amount of cerebral oxygen required is taken care of thanks to the cerebral blood flow. In the immature brain where the coupling is not in place, cerebral blood is instead mined for its oxygen. If a sudden rise in the amount of cerebral oxygen required occurs, for instance, there is an increase in the amount of oxygen extracted from the blood. Though this mechanism is also used in the mature brain, it is secondary to the fundamental flow-metabolism coupling, which governs the situation. In the immature brain however, it seems that the dependence on oxygen extraction from the blood is much more important.

The study is crucial especially when considering that as many as 25-53% of those born at <28 weeks gestation are treated with intravenous dopamine. It does seem somewhat lacking then that until now, the actual physiological effect of dopamine with respect to flow-metabolism coupling was unknown. Keeping in mind that intravenous dopamine can cross the immature blood-brain barrier (BBB) of the immature brain of a preterm infant, knowing how dopamine works may be a stepping stone to further studies which tell us exactly how much dopamine should be administered in preterm infants. Indeed, too much dopamine accumulated in the brain may have harmful effects as the neurohormone has been linked to psychosis and schizophrenia.

Finally, the study may not only be beneficial to preterm infants. The findings may also be relevant to adults suffering from pathological conditions affecting both flow-metabolism coupling and BBB permeability, such as ischemic stroke.

So, undergrads, when you recite the roles and functions of dopamine in humans, don't curse the researchers who are responsible for the findings. Because it turns out that dopamine can save lives.

Image credits: Sbrools (via Wikimedia Commons) and jdsmith1021 (via Flickr).

Reference: Wong, F.Y., Barfield, C.P., Horne, R.S.C. & Walker, A.M. Dopamine therapy promotes cerebral flow-metabolism coupling in preterm infants. Intensive Care Medicine 35, 1777-1782 (2009).