The mesenteric circulation is a “pressure-passive” system. Its blood flow and oxygen extraction are primarily regulated by the intestine's metabolic demands. Autoregulation plays only a minor role in its control in both the fed and fasted state (1
). The introduction of feedings into the intestinal tract increases its metabolic requirements and increases its oxygen uptake (1
). In the adult, the intestine's increased postprandial oxygen uptake is initially achieved by an increase in blood flow. This is followed by an increase in oxygen extraction as the postprandial hyperemia wanes (2
Although a left-to-right aortopulmonary shunt has a profound impact on mesenteric perfusion (24
), full term infants, with systemic-to-pulmonary arterial shunts, are able to maintain their mesenteric blood flow, both at rest and during feedings, by vasodilating their splanchnic circulation (24
). The immature infant, on the other hand, has a limited ability to increase its mesenteric blood flow and oxygen extraction at rest (3
). Prior studies have shown that, during the fasting state, a left-to-right PDA shunt causes a decrease in arterial perfusion pressure, an increase in localized mesenteric vascular resistance, and a decrease in mesenteric blood flow (8
The presence of a PDA produces similar changes in other “pressure-passive” vascular beds; however, the presence of a PDA does not necessarily impede their ability to increase local perfusion when metabolic demand increases. For example, the presence of a PDA decreases blood flow to resting skeletal muscle by nearly 50% (25
). However, once the muscle starts to contract, its vascular resistance decreases precipitously and blood flow increases markedly. As a result, blood flow, oxygen delivery and muscle performance are the same whether the ductus is open or closed (25
Our findings in the mesenteric circulation, contrast markedly with what has been observed in skeletal muscle. We found that preterm baboons, with a moderate PDA shunt, have lower systemic BP, lower mean and diastolic SMA velocities, and increased PI during the baseline, preprandial period (, and ). Preterm animals, with a closed ductus, are able to increase their SMA velocities and decrease their relative resistance index following a feeding (); in contrast, animals with an open ductus are not able to make the same compensatory changes ().
The inability to increase postprandial flow, in the presence of a PDA, may increase the risk for intestinal ischemia, feeding intolerance, and NEC (5
). Although it is unlikely that a PDA is sufficient to produce the ischemic injury itself, the inability to increase flow following a feeding might render the intestine more vulnerable to other cardiovascular stresses or ischemic insults. For example, small increases in intra-abdominal pressure (produced by increased diaphragmatic breathing) have no effect on intestinal blood flow in newborn animals with a closed ductus; in contrast, in the presence of a PDA, the same changes in intra-abdominal pressure lead to decreased intestinal blood flow (25
). This hypothesis is consistent with the study by Palder et al (27
), which showed that the severity of NEC was increased in the presence of a PDA.
Several caveats are needed when interpreting our results. The two animal groups were not randomly chosen. They were comprised of those that spontaneously closed their ductus before day 10 and those that failed to close their ductus by that date. Therefore, our experimental design does not allow us to determine whether the differences between the groups are due to the PDA shunt, itself, or to factors that might coexist in animals that fail to close their ductus spontaneously. Although the distribution of several factors known to affect the postprandial, hyperemic response (e.g., initial degree of illness and postnatal age (28
), prior exposure to feedings (11
), feeding volume (22
), exposure to phototherapy (30
), and degree of mechanical ventilation at the time of study (21
)) were similar between the two groups, other unknown conditions may have contributed to our findings. Our experimental model, also, does not allow us to comment on the role of a PDA with larger feeding volumes, or of the immature intestine's ability to increase its oxygen extraction. It should also be noted that the investigator who performed the hemodynamic assessments was not blinded to the status of the ductus shunt. This may have introduced an unconscious bias when performing the SMA-specific hemodynamic measurements.
There are also several differences between our results in baboons and those that have been reported in humans. In general, the postprandial hyperemic response in the baboon was of shorter duration than that observed in the human (10
). The PDA shunts in our animals were only moderate in size; and, none of the animals developed NEC. In addition, none of the animals had reversal of flow in the descending aorta or mesenteric bed. In contrast, reversal of flow has been observed in the human studies (10