Pediatric Pulmonology 42:505–512 (2007) Lung Tissue Mechanics Predict Lung Hypoplasia in a Rabbit Model for Congenital Diaphragmatic Hernia Andreas W. Flemmer, MD, 1 Jacques C. Jani, MD, 2,4 Florian Bergmann, MD, 3 Oliver J. Muensterer, MD, PhD, 3,5 Denis Gallot, MD, PhD, 2 Kerstin Hajek, 1 Junichi Sugawara, MD, 2 Holger Till, MD, PhD, 3,5 and Jan A. Deprest, MD, PhD 2,4 * Summary. Several animal models have been proposed to study the pathophysiology of congenital diaphragmatic hernia (CDH). Surgical induction of CDH in fetal rabbits during the pseudoglandular phase has been shown to induce severe pulmonary hypoplasia, but functional studies in this model are scarce. We aimed to measure neonatal pulmonary impedance and related it to the severity of lung hypoplasia. CDH was surgically created in rabbits at 23 days of gestation. Following cesarean delivery at term (31 days) pups were subjected to measurement of total lung capacity (TLC), lung to body weight ratio (LBWR) and lung impedance by forced oscillation technique (FOT). Airway resistance (R aw ), tissue elastance (H L ), tissue damping (G L ), and hysteresivity (h) (G L /H L ) were calculated from impedance data. Twelve CDH fetuses and 15 controls were available for final analysis. LBWR and TLC were significantly lower in the CDH group compared to gestational and age matched controls (P < 0.001). R aw ,H L , and G L were significantly increased in CCDH fetuses. h and H L best reflected lung hypoplasia (LBWR) (r 2 ¼ 0.42 and 0.43; P ¼ 0.001), indicating a dominant contribution of lung tissue mechanics to CDH-induced lung hypoplasia. We successfully introduced lung impedance measurement by FOT in neonatal rabbits. Following surgical induction of CDH in the pseudoglandular phase, they have, next to morphological evidence of pulmonary hypoplasia, changes in lung mechanics. Our results for lung tissue mechanics support the concept of delayed pulmonary tissue modeling. We propose to employ functional studies in future experiments when evaluating prenatal interventions aimed at reversing pulmonary hypoplasia. Pediatr Pulmonol. 2007; 42:505–512. ß 2007 Wiley-Liss, Inc. Key words: diaphragmatic hernia; elastance; hysteresivity; rabbit model; lung hypoplasia. INTRODUCTION Despite progress in neonatal care, congenital diaphrag- matic hernia (CDH) is still associated with a high perinatal mortality, mainly due to pulmonary hypoplasia and/or pulmonary hypertension. Attempts to improve outcome in human neonates by prenatal interventions are subject to extensive research and have already shown promising results. 1–3 So far, the effects of prenatal and postnatal therapies on the lung development have been investigated morphologically 4–6 and functionally with regard to the compliance of the respiratory system. 7,8 On pathological examination, hypoplastic lungs in CDH patients and in animal models show lower numbers and lesser generations of airways, thickened alveolar septa and an abnormal architecture of the respiratory acinus. 9–11 The vascular bed is reduced as well, with a decreased number of pulmo- nary arteries per unit lung volume. 12,13 Intrapulmonary arteries are excessively and more peripherally muscular- ized down to the level of small intra-acinar arterioles. 5 It has been shown, that human neonates as well as fetal sheep with surgically induced CDH have poor lung 1 Division of Neonatology, University Children’s Hospital, Perinatal Center, Ludwig-Maximilian-University Munich, Grosshadern, Germany. 2 Center for Surgical Technologies, Faculty of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium. 3 Department of Pediatric Surgery, Ludwig-Maximilians-University Munich, Munich, Germany. 4 Department of Obstetrics and Gynaecology, Leuven, Belgium. 5 Department of Pediatric Surgery, University Leipzig, Leipzig, Germany. Grant sponsor: European Commission in its 5th Framework Programme; Grant number: QLG1 CT2002 01632; EuroTwin2Twin; Grant sponsor: Fonds Wetenschappelijk Onderzoek Vlaanderen; Grant number: G.0378.02. *Correspondence to: Jan A. Deprest, M.D., Ph.D., Department of Obstetrics and Gynaecology, Unit of Prenatal and Gynaecological Ultrasound and Fetal Therapy, UZ Gasthuisberg, 3000 Leuven. E-mail: Jan.Deprest@uz.kuleuven.be Received 14 November 2006; Revised 8 March 2007; Accepted 8 March 2007. DOI 10.1002/ppul.20618 Published online in Wiley InterScience (www.interscience.wiley.com). ß 2007 Wiley-Liss, Inc.