Systemic arteriovenous fistula leads to pulmonary artery remodeling and  abnormal vasoreactivity in the fetal lamb

Jouannic, Jean‐Marie; Roussin, Régine; Hislop, Alison A.; Martinovic, Jéléna; Boczkowski, Jorge; Dinh-Xuan, Anh Tuan

doi:10.1152/ajplung.00369.2002

Cited by 16 publications

(11 citation statements)

References 34 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other models, creating left to right shunts in young animals [16,23,24] might have advantages with respect to affecting flow and pressure in the pulmonary arteries comparable with the situation in congenital heart disease. However, the increase in PAP in these models is moderate and, until now, they failed to display the more advanced lesions of pulmonary arterial hypertension.…”

Section: Limitations Of the Studymentioning

confidence: 99%

The role of increased pulmonary blood flow in pulmonary arterial hypertension

Albada¹,

Schoemaker²,

Kemna³

et al. 2005

Eur Respir J

View full text Add to dashboard Cite

Chronic increased pulmonary blood flow is considered a pre-requisite for the induction of advanced vascular lesions in pulmonary arterial hypertension in congenital heart defects. The aim of the present study was to characterise the effects of increased pulmonary flow induced by an aortocaval shunt in the monocrotaline rat model for pulmonary hypertension in terms of survival, haemodynamics, pathology and histology.Male Wistar rats were injected with monocrotaline followed by the creation of an abdominal aortocaval shunt. Animals were sacrificed when displaying symptoms of weight loss or dyspnoea, 4-5 weeks after the creation of the shunt.Echocardiography identified increased ventricular dimensions in shunted rats and right ventricular hypertrophy in monocrotaline-treated rats. At similar pulmonary artery pressures, shunted monocrotaline rats displayed higher morbidity and mortality, increased pulmonary-tosystemic artery pressure ratios and increased right ventricular hypertrophy compared with nonshunted monocrotaline rats. Histological assessment demonstrated increased number and diameter of pre-acinar pulmonary arteries. Intra-acinar vessel remodelling and occlusion occurred to a similar extent in shunted and nonshunted monocrotaline rats.In conclusion, increased pulmonary blood flow in monocrotaline-induced pulmonary hypertension is associated with increased morbidity, mortality, and unfavourable haemodynamic and cardiac effects. These effects could be attributed to more pronounced right heart failure rather than to altered intra-acinar pulmonary vessel remodelling. KEYWORDS: Animal model, congenital heart disease, plexogenic arteriopathy, pulmonary arterial hypertension, pulmonary vascular histopathology, right heart failure P atients with congenital heart disease associated with systemic-to-pulmonary shunts, increasing both pulmonary blood flow and pressure, develop characteristic pulmonary vascular lesions as concentric-laminar intimal fibrosis and plexiform lesions. These vascular lesions are characterised by vascular smooth muscle and endothelial cell proliferation. In contrast, in patients with congenital heart defects and isolated increased pulmonary artery pressure (PAP), these lesions almost never develop [1,2]. The current authors hypothesise that, in congenital heart defects, increased pulmonary blood flow, in addition to increased pressure, is a pre-requisite for the development of the hallmark lesions of advanced pulmonary arterial hypertension.Animal models with an isolated increase in PAP, e.g. induced by the toxic alkaloid monocrotaline, show pulmonary vascular remodelling, but fail to display the more advanced lesions as described previously [3-5].The role of increased pulmonary blood flow has been explored in animal models [6]. In rat models with isolated increased flow [7,8], a moderate increase in pulmonary pressure and medial hypertrophy has been observed, but only after a prolonged period of exposure.When the additional effect of flow was explored in existing rat models for pul...

show abstract

Section: Limitations Of the Studymentioning

confidence: 99%

The role of increased pulmonary blood flow in pulmonary arterial hypertension

Albada¹,

Schoemaker²,

Kemna³

et al. 2005

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…Jouannic et al (28) have shown that the prenatal creation of an SAVF not only increased pulmonary arterial blood pressure and resistance but also led to structural pulmonary arterial remodeling and altered pulmonary vascular reactivity. Those striking changes in the fetal vascular bed, including increased number of peripheral muscular arteries together with an increase in pulmonary arterial medial thickness, were not associated with pulmonary arterial high blood flow at birth.…”

Section: Discussionmentioning

confidence: 99%

“…More recently Jouannic et al (27) have designed an experimental model of surgically created SAVF in the fetal lamb. They found that, at birth, there was an increase in pulmonary arterial pressure and resistance with no increase in pulmonary arterial blood flow (28). This was associated with striking structural remodeling of the pulmonary vascular bed similar to the pulmonary structural abnormalities found in neonates who died with PPH (23,31).…”

mentioning

confidence: 85%

“…Animals received care in accordance with the "Principles of Laboratory Animal Care" and the "Guide for the Care and Use of Laboratory Animals" (5) and under the authority of the French Ministry of Agriculture. Physiological measurements including flow and pressure measurements and blood gas and pH determination were as described previously in detail (28).…”

Section: Methodsmentioning

confidence: 99%

“…At 134 -139 days the ewes underwent a second laparotomy. Measurement of pressure and flow in the left pulmonary artery (LPA) have previously been described elsewhere (27,28). Briefly, the fetal heart and great vessels were exposed through a left thoracotomy.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Surfactant phospholipids and proteins are increased in fetal sheep with pulmonary hypertension secondary to fetal systemic arteriovenous fistula

Benachi¹

2005

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

2004.-To determine whether prenatal surfactant storage was altered in a model of systemic arteriovenous fistula (SAVF) with pulmonary hypertension, a fistula was created between the internal jugular vein and the carotid artery in 120-day fetal lambs, and surfactant material was explored at 134 days. Total phospholipids (TPL) and disaturated phosphatidylcholine (DSPC) were increased in whole lung tissue. Phospholipid analysis of isolated lamellar body fraction evidenced a specific increase of surfactant pool size: TPL and DSPC in this fraction were enhanced 1.9 and 2.9 times, respectively, when referred to DNA. Although the steady-state level of transcripts of surfactant protein (SP)-A and SP-B was not found to be changed at the time of death, semiquantitative Western blot analysis revealed elevated SP-A and SP-B protein contents three-and twofold, respectively. These findings indicate markedly enhanced accumulation of surfactant material in the presence of surgically induced prenatal pulmonary hypertension. Although total lung cell number was increased by 26%, SP-B immunolabeling indicated that increased surfactant amount did not result from an increased alveolar type II cell proportion, but rather from an increased rate of storage. Whether similar changes in surfactant are encountered in human neonates with persistent pulmonary hypertension is worthy of investigation. fetus; lung surfactant; alveolar type II cells; disaturated phosphatidylcholine SYSTEMIC ARTERIOVENOUS FISTULA (SAVF) is a rare condition in the fetus that is known to be associated with persistent pulmonary hypertension (PPH) at birth. The newborn displays elevated pulmonary arterial pressure, abnormal pulmonary vascular reactivity, and high pulmonary vascular resistance leading to severe hypoxemia. Fetuses with vein of Galen arteriovenous malformation (14), highly vascularized sacrococcygeal teratoma, or chorioangioma are at risk of developing severe cardiac failure and PPH. To our knowledge, no studies have paid attention to the surfactant components in those neonates, probably because most of them were delivered prematurely due to severe heart failure and also because PPH is the primary concern. Because such studies can not readily be performed in humans, animal models of PPH may help in exploring surfactant material in this condition. Several experimental models of fetal pulmonary hypertension have been described over the past 15 years. Chronic intrauterine hypoxia (1), constriction (2), or ligation (31) of the ductus arteriosus induced pulmonary hypertension in the fetal lamb. In utero placement of aortopulmonary shunts in fetal lambs has also been shown to cause pulmonary hypertension at birth (34). More recently Jouannic et al. (27) have designed an experimental model of surgically created SAVF in the fetal lamb. They found that, at birth, there was an increase in pulmonary arterial pressure and resistance with no increase in pulmonary arterial blood flow (28). This was associated with striking structural remodeling of the pulmonary vascul...

show abstract