Neonatal cardiopulmonary transition in an ovine model of congenital diaphragmatic hernia

Abstract

ObjectiveInfants with a congenital diaphragmatic hernia (CDH) are at high risk of developing pulmonary hypertension after birth, but little is known of their physiological transition at birth. We aimed to characterise the changes in cardiopulmonary physiology during the neonatal transition in an ovine model of CDH.MethodsA diaphragmatic hernia (DH) was surgically created at 80 days of gestational age (dGA) in 10 fetuses, whereas controls underwent sham surgery (n=6). At 138 dGA, lambs were delivered via caesarean section and ventilated for 2 hours. Physiological and ventilation parameters were continuously recorded, and arterial blood gas values were measured.ResultsDH lambs had lower wet lung-to-body-weight ratio (0.016±0.002vs0.033±0.004), reduced dynamic lung compliance (0.4±0.1mL/cmH2O vs1.2±0.1 mL/cmH2O) and reduced arterial pH (7.11±0.05vs7.26±0.05), compared with controls. While measured pulmonary blood flow (PBF) was lower in DH lambs, after correction for lung weight, PBF was not different between groups (4.05±0.60mL/min/gvs4.29±0.57 mL/min/g). Cerebral tissue oxygen saturation was lower in DH compared with control lambs (55.7±3.5vs67.7%±3.9%).ConclusionsImmediately after birth, DH lambs have small, non-compliant lungs, respiratory acidosis and poor cerebral oxygenation that reflects the clinical phenotype of human CDH. PBF (indexed to lung weight) was similar in DH and control lambs, suggesting that the reduction in PBF associated with CDH is proportional to the degree of lung hypoplasia during the neonatal cardiopulmonary transition.

Antenatal sildenafil treatment improves neonatal pulmonary hemodynamics and gas exchange in lambs with diaphragmatic hernia

“…Most studies have found no difference 25,29,33,40 , one reported a decrease 27 and two studies reported an increase in lung weight 26,30 . While there was no significant difference between the two groups in our study, we found that DH lambs treated with sildenafil tended (P = 0.06) to have greater LBWR than did untreated DH lambs, but the lungs were still markedly hypoplastic in both treated (48% of historical controls) and untreated (39%) DH lambs 34 . Indeed, while dynamic lung compliance was initially (during the first 20 min) better in sildenafil-treated DH lambs, by the end of the 120-min ventilation period it was no longer different between the two groups.…”

“…We have previously shown that pulmonary blood flow (PBF) in sham‐operated controls is 2.4‐fold greater than in DH lambs. Based on the variability in that study, we determined that at least six successful animals per group would provide power of ≥ 80% with a two‐sided type‐I error of 5% to detect a 1.5‐fold increase in PBF in DH‐sildenafil lambs compared with DH‐saline lambs.…”

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

“…All surgical procedures were performed under general anaesthesia using intravenous sodium thiopental (Pentothal; Jurox, New Zealand) for induction and inhaled isoflurane (≈2% in room air; Isoflow, Abbot) for maintenance. Ewes (Merino X Border-Leicester) were intubated and monitored (ECG, expired CO 2 , arterial oxygen saturation (SaO 2 )) during surgery 14…”

“…At ≈80 days gestational age (dGA; term≈147 dGA), a DH was surgically created in fetal lambs as previously described 14. Following maternal midline laparotomy and hysterotomy, the fetal chest was exteriorised and incised through the left ninth intercostal space.…”

“…At ≈138 dGA, ewes and their fetuses were anaesthetised and the lambs instrumented prior to caesarean section delivery as previously described 14. Briefly, lambs were partially exteriorised and intubated with a clamped endotracheal tube (size 4.0) prior to instrumentation to prevent lung aeration.…”