Lung hypoplasia in newborn rabbits with a diaphragmatic hernia affects pulmonary ventilation but not perfusion

Abstract

BackgroundA congenital diaphragmatic hernia (DH) can result in severe lung hypoplasia that increases the risk of morbidity and mortality after birth; however, little is known about the cardiorespiratory transition at birth.MethodsUsing phase-contrast X-ray imaging and angiography, we examined the cardiorespiratory transition at birth in rabbit kittens with DHs. Surgery was performed on pregnant New Zealand white rabbits (n=18) at 25 days' gestation to induce a left-sided DH. Kittens were delivered at 30 days' gestation, intubated, and ventilated to achieve a tidal volume (V_t) of 8 ml/kg in control and 4 ml/kg in DH kittens while they were imaged.ResultsFunctional residual capacity (FRC) recruitment and V_t in the hypoplastic left lung were markedly reduced, resulting in a disproportionate distribution of FRC into the right lung. Following lung aeration, relative pulmonary blood flow (PBF) increased equally in both lungs, and the increase in pulmonary venous return was similar in both control and DH kittens.ConclusionThese findings indicate that nonuniform lung hypoplasia caused by DH alters the distribution of ventilation away from hypoplastic and into normally grown lung regions. During transition, the increase in PBF and pulmonary venous return, which is vital for maintaining cardiac output, is not affected by lung hypoplasia.

Figure 1

Phase-contrast X-ray (PCX) images of (a) a kitten with a left-sided diaphragmatic hernia (DH); (b) control kitten; (c) a kitten with a left-sided DH using angiography to show the pulmonary arterial tree; (d) a control kitten using angiography to show the pulmonary arterial tree; (e) a DH kitten using angiography to image the foramen ovale (FO); and (f) a control kitten using angiography to image the left ventricle (LV) and quantify pulmonary venous return.

Figure 2

Computed tomographic three-dimensional reconstruction of lungs from a diaphragmatic hernia (DH) kitten and a control kitten. In DH kittens, the right lung (light red) appeared unaffected, whereas the left upper lobe (green) was slightly reduced in size and the left lower lobe (blue) was markedly reduced in size.

Figure 3

Measures of total functional residual capacity (FRC; a) and the temporal pattern of FRC recruitment in the left (hypoplastic; dark gray) and right (light gray) lungs of control (b) and diaphragmatic hernia (DH; c) kittens. The temporal pattern of FRC recruitment is displayed as the time taken to reach 20–100% of the measured FRC for each lung (mean±SEM, *P<0.05).

Figure 4

The tidal volume (a) in control (light gray) and diaphragmatic hernia (DH; dark gray) lungs and the distribution of tidal volume between the left (hypoplastic; light gray) and right (dark gray) lungs of control (b) and DH (c) kittens (mean±SEM, *P<0.05).

Figure 5

The proportional distribution of functional residual capacity (FRC; a), incoming tidal volume (b), and peak inflation volumes (c) in kittens with a diaphragmatic hernia (DH; dark gray) and in control kittens (light gray; mean±SEM, *P<0.05). LL, lower left lung; LR, lower right lung; UL, upper left lung; UR, upper right lung.

Figure 6

Relative measures of (a) right-to-left blood flow through the foramen ovale, (b) pulmonary venous return and blood flow in the left (e) and right (f) pulmonary arteries (PAs), as well as measures of blood flow transit times in the left (c) and right (d) pulmonary arteries (PAs)s in diaphragmatic hernia (DH; dark gray) and control kittens (light gray). BVent indicates measurements prior to ventilation, AVent1-3 indicate measurements after the first transitional breaths.