Pulmonary hemodynamic responses to in utero ventilation in very immature fetal sheep

Abstract

Background: The onset of ventilation at birth decreases pulmonary vascular resistance (PVR) resulting in a large increase in pulmonary blood flow (PBF). As the large cross sectional area of the pulmonary vascular bed develops late in gestation, we have investigated whether the ventilation-induced increase in PBF is reduced in immature lungs.

Methods: Surgery was performed in fetal sheep at 105 d GA (n = 7; term ~147 d) to insert an endotracheal tube, which was connected to a neonatal ventilation circuit, and a transonic flow probe was placed around the left pulmonary artery. At 110 d GA, fetuses (n = 7) were ventilated in utero (IUV) for 12 hrs while continuous measurements of PBF were made, fetuses were allowed to develop in utero for a further 7 days following ventilation.

Results: PBF changes were highly variable between animals, increasing from 12.2 ± 6.6 mL/min to a maximum of 78.1 ± 23.1 mL/min in four fetuses after 10 minutes of ventilation. In the remaining three fetuses, little change in PBF was measured in response to IUV. The increases in PBF measured in responding fetuses were not sustained throughout the ventilation period and by 2 hrs of IUV had returned to pre-IUV control values.

Discussion and conclusion: Ventilation of very immature fetal sheep in utero increased PBF in 57% of fetuses but this increase was not sustained for more than 2 hrs, despite continuing ventilation. Immature lungs can increase PBF during ventilation, however, the present studies show these changes are transient and highly variable.

Figure 1

The ventilation circuit (white tubes) was connected to the endotracheal tube via a "Y" piece. An additional catheter was inserted into the upper trachea (black tube) and directed toward the glottis. All catheters were exteriorized via a flank incision. The upper tracheal catheter was connected to the ventilation circuit creating an exteriorized 'tracheal loop' to allow normal flow of lung liquid.

Figure 2

Fetal blood gas status before and during in utero ventilation (IUV). Graphs show the Mean ± SEM for pH, PaCO₂, PaO₂ and SaO₂ for fetuses before and during 12 hrs of in utero ventilation (n = 7; black circles). Values are compared to 110 d fetuses (sham operated controls completed for previous study n = 5; white circles). Asterisks indicate statistical difference between IUV and control fetuses.

Figure 3

Changes in pulmonary blood flow (PBF) with in utero ventilation (IUV). A) PBF (mL/min) measured in the left pulmonary artery of IUV exposed fetuses (n = 7) pre-IUV, following lung liquid drainage (LLD) and throughout IUV. Asterisks indicate values which are significantly different from pre-IUV values (p < 0.001). B) PBF (mL/min) measured in the left pulmonary artery after sub-division of fetuses into responders (open circles, n = 4) and non-responders (closed circles, n = 3); values were measured pre-IUV, following lung liquid drainage (LLD) and throughout IUV. Asterisks indicate values which are significantly different between responding and non-responding fetuses (p < 0.001).

Figure 4

Pulmonary blood flow (PBF) waveforms. Individual PBF waveforms are shown for non-responding (left) and responding (right) fetuses. Two sets of waveforms are displayed the first taken during the fetal period and the second during in utero ventilation (enclosed in the square).

Figure 5

Changes in heart rate with in utero ventilation (IUV). A) Values represent % increase in heart rate above control values of IUV exposed fetuses (n = 7) pre-IUV, following lung liquid drainage (LLD) and throughout IUV. B) Values represent % increase in heart rate above control values in responding (open circles, n = 4) and non-responders (closed circles, n = 3) IUV fetuses; values were measured pre-IUV, following lung liquid drainage (LLD) and throughout IUV.