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 (Vt) of 8 ml/kg in control and 4 ml/kg in DH kittens while they were imaged.ResultsFunctional residual capacity (FRC) recruitment and Vt 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.

Neonatal cardiopulmonary transition in an ovine model of congenital diaphragmatic hernia

“…Thus, the primary mechanism for the higher PVR and lower uncorrected PBF in DH lambs seems mostly due to a smaller lung rather than an abnormal vasodilatory response. This result is also consistent with our previous finding in DH rabbits and indicates that any pulmonary vessel smooth muscle hypertrophy and neomuscularisation that may have occurred prenatally does not directly impact on the capacity of the vessels to vasodilate in response to lung aeration 13…”

“…We aimed to describe the cardiopulmonary physiology during transition to neonatal life in lambs with pulmonary hypoplasia due to a diaphragmatic hernia (DH). In DH rabbit kittens, we have recently found that the increase in pulmonary arterial blood flow (PBF) induced by lung aeration in the normal lung also occurs in the hypoplastic lung 13. Therefore, in this study, we hypothesised that abnormal lung development may predispose DH lambs to low lung compliance and respiratory insufficiency, but any reduction in pulmonary blood flow during the transition period will be proportional to the reduction in lung size.…”

Effects of tracheal occlusion on the neonatal cardiopulmonary transition in an ovine model of diaphragmatic hernia

“…These authors hypothesised that ongoing alveolar recruitment eventually matched ventilation and perfusion after prolonged ventilation. This hypothesis is supported by our previous observation that functional residual capacity and V T recruitment are significantly slower in DH lungs 40. Furthermore, in this study, we observed a steady improvement in arterial pH values (and declining trend in PaCO 2 and A–aDO 2 ) at the end of the experiment in FETO lambs, in contrast to the progressive decline observed in DH lambs.…”

Physiologically based cord clamping improves cardiopulmonary haemodynamics in lambs with a diaphragmatic hernia

“…In normal term infants, lung aeration occurs rapidly and so ICC results in only a limited interruption to cardiac output and gas exchange at birth. In contrast, CDH infants have stiff, hypoplastic lungs which are likely to take much longer to aerate, as has been demonstrated experimentally 12. As lung aeration stimulates the increase in PBF, it is not surprising that the increase in PBF is also delayed in newborn lambs with lung hypoplasia 13.…”