Prenatal dexamethasone rescues heart hypoplasia in fetal rats with congenital diaphragmatic hernia

Migliazza, Lucia; Xia, Huimin; Arnaiz, A; Alvarez, Juan; Alfonso, Luisa F.; Díez-Pardo, Juan A.; Soler, Adolfo Valls; Tovar, Juan A.

doi:10.1053/jpsu.2000.19243

Cited by 10 publications

(4 citation statements)

References 32 publications

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“…The reduction in the heart size corresponds to hypoplasia rather than to atrophy, because wet-dry weight and DNA-to-protein ratios were similar in CDH and control groups, according to studies in the lamb model of CDH 18 . Furthermore, it was shown that prenatal dexamethasone rescues in part heart hypoplasia in fetal rats with CDH 19 , and intrauterine correction of surgically created CDH late in gestation reversed cardiac hypoplasia in the of fetal lamb model 12,20 . However, tracheal ligation in this animal model could not reverse the left ventricular hypoplasia, and this was interpreted as probably caused by the ongoing heart compression promoted by the expanding lung in the tracheal ligated fetus, as we also showed in this rabbit model of CDH 4,5 .…”

Section: Discussionmentioning

confidence: 99%

Heart hypoplasia in an animal model of congenital diaphragmatic hernia

Tannuri

2001

Rev. Hosp. Clin.

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Purpose:In previous papers, we described a new experimental model of congenital diaphragmatic hernia in rabbits, and we also reported noninvasive therapeutic strategies for prevention of the functional and structural immaturity of the lungs associated with this defect. In addition to lung hypoplasia, pulmonary hypertension, biochemical, and structural immaturity of the lungs, the hemodynamics of infants and animals with congenital diaphragmatic hernia are markedly altered. Hence, cardiac hypoplasia has been implicated as a possible cause of death in patients with congenital diaphragmatic hernia, and it is hypothesized to be a probable consequence of fetal mediastinal compression by the herniated viscera. Cardiac hypoplasia has also been reported in lamb and rat models of congenital diaphragmatic hernia. The purpose of the present experiment was to verify the occurrence of heart hypoplasia in our new model of surgically produced congenital diaphragmatic hernia in fetal rabbits.Methods: Twelve pregnant New Zealand rabbits underwent surgery on gestational day 24 or 25 (normal full gestational time -31 to 32 days) to create left-sided diaphragmatic hernias in 1 or 2 fetuses per each doe. On gestational day 30, all does again underwent surgery, and the delivered fetuses were weighed and divided into 2 groups: control (non-surgically treated fetuses) (n = 12) and congenital diaphragmatic hernia (n = 9). The hearts were collected, weighed, and submitted for histologic and histomorphometric studies.Results: During necropsy, it was noted that in all congenital diaphragmatic hernia fetuses, the left lobe of the liver herniated throughout the surgically created defect and occupied the left side of the thorax, with the deviation of the heart to the right side, compressing the left lung; consequently, this lung was smaller than the right one. The body weights of the animals were not altered by congenital diaphragmatic hernia, but heart weights were decreased in comparison to control fetuses. The histomorphometric analysis demonstrated that congenital diaphragmatic hernia promoted a significant decrease in the ventricular wall thickness and an increase in the interventricular septum thickness.Conclusion: Heart hypoplasia occurs in a rabbit experimental model of congenital diaphragmatic hernia. This model may be utilized for investigations in therapeutic strategies that aim towards the prevention or the treatment of heart hypoplasia caused by congenital diaphragmatic hernia. DESCRIPTORS: Congenital diaphragmatic hernia. Heart. Hypoplasia. Fetus.In previous papers, we have described a new experimental model of congenital diaphragmatic hernia (CDH) in rabbits, and we also have reported on studies of noninvasive therapeutic strategies for prevention of functional and structural immaturity of lungs associated with this defect. These strategies consist of prenatal intra-amniotic administration of porcine surfactant or dexamethasone and prenatal tracheal ligation (TL), an invasive method that effectively treats or prevents pulmonary...

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Section: Discussionmentioning

confidence: 99%

Heart hypoplasia in an animal model of congenital diaphragmatic hernia

Tannuri

2001

Rev. Hosp. Clin.

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“…Glucocorticoid administration improves contractile performance of the heart (21–25), and glucocorticoids inhibit cardiomyocyte apoptosis triggered by ischemia, cytokines, and cardiotoxic drugs (doxorubicin) (26–30). Prenatal exposure to glucocorticoids improves cardiovascular function in the newborn immediately after birth (31, 32). Conversely, elevated levels of glucocorticoids have also been linked to a variety of negative cardiac outcomes.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid signaling in the heart: A cardiomyocyte perspective

Oakley

Cidlowski

2015

The Journal of Steroid Biochemistry and Molecular Biology

104

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Heart failure is one of the leading causes of death in the Western world. Glucocorticoids are primary stress hormones that regulate a vast array of biological processes, and synthetic derivatives of these steroids have been mainstays in the clinic for the last half century. Abnormal levels of glucocorticoids are known to negatively impact the cardiovascular system; however, surprisingly little is known about the direct role of glucocorticoid signaling in the heart. The actions of glucocorticoids are mediated classically by the glucocorticoid receptor (GR). In certain cells, such as cardiomyocytes, glucocorticoid occupancy and activation of the mineralocorticoid receptor (MR) may also contribute to the observed response. Recently, there has been a surge of reports investigating the in vivo function of glucocorticoid signaling in the heart using transgenic mice that specifically target GR or MR in cardiomyocytes. Results from these studies suggest that GR signaling in cardiomyocytes is critical for the normal development and function of the heart. In contrast, MR signaling in cardiomyocytes participates in the development and progression of cardiac disease. In the following review, we discuss these genetic mouse models and the new insights they are providing into the direct role cardiomyocyte glucocorticoid signaling plays in heart physiology and pathophysiology.

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“…Fetal exposure to an excess of glucocorticoids has been implicated as a causative factor in fetal growth restriction called intrauterine growth retardation (IUGR) [5]. The effects of prenatal Dex therapy on the fetal skeletal system need to be clarified because this kind of therapy can result in more disadvantages than advantages, especially in the long-term consequences in postnatal life and adulthood [1,[4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%