Structural immaturity of the heart in congenital diaphragmatic hernia in rats

Purpose: The form and function of the heart are the final result of an inte gration of cells, tissues, and extracellular material. The extracellular ma trix (ECM) is a complex array of different molecular components, and it pla ys an important role for the transfer of mechanical force in both contracti on and relaxation phases in the cardiac cycle. ECM plays also a significant role in the development of the heart. The aim of this study was to evaluat e the expression of important ECM components in the heart of rats with indu ced CDH to test the hypothesis that an alteration of ECM may contribute to the cardiac maldevelopment, which recently has been identified as a contrib utive factor far the high mortality rate in babies with congenital diaphrag matic hernia (CDH). Methods: CDH model was induced in pregnant rats after administration of 100 mg of nitrofen on day 9.5 of gestation (term, 22 days), In control animals the same dose of olive oil was given without nitrofen. Cesarean section wa s performed on day 21 of gestation. The fetuses were divided into 2 groups: normal control (n = 10) and nitrofen-induced CDH (n = 10). Reverse transcr iption polymerase chain reaction (RT-PCR) was performed to evaluate the rel ative amount of tropoelastin and alpha1 (1) procollagen mRNA expression. El astin protein content was measured using enzyme-linked immunosorbent assay (ELISA). Results: There was a reduction in tropoelastin mRNA (P < .05) and procollag en mRNA (P < .05) in CDH compared with controls. The cardiac alpha -elastin content also was reduced in CDH (P < .01). Conclusions: The reduced cardiac tropoelastin and procollagen gene expressi on and the reduced <alpha>-elastin content indicate that the heart in CDH s tructurally is immature. The reduced production of cardiac ECM may contribu te to a contractile dysfunction, which makes the heart unable to respond to the hemodynamic load accompanying persistent pulmonary hypertension (PPH). J Pediatr Surg 36:770-773. Copyright (C) 2001 by W.B. Saunders Company.