Cavopulmonary anastomosis is used for palliation of cyanotic cardiac lesions. Postoperative development of pulmonary arteriovenous malformations can be significant in 10% to 25% of patients. To study the basis for formation of arteriovenous malformations, we developed an ovine model that reliably induces their development 8 weeks after cavopulmonary anastomosis. Previously, we found that cavopulmonary anastomosis inhibits the expression of pulmonary angiotensin-converting enzyme and suppresses angiotensin II production.
This study examines the role of the angiotensin II receptors, type 1 and type 2, in this setting of pulmonary vascular remodeling.
Lambs, aged 40 to 50 days, underwent cavopulmonary anastomosis. In age-matched control animals, a sham operation was performed. Messenger RNA and protein expression in lung specimens was measured at successive time points after cavopulmonary anastomosis or sham operations (n = 3 at each time point).
Angiotensin type 1 mRNA was maximally upregulated 2-fold at 5 weeks after cavopulmonary anastomosis (P =.006). Expression of angiotensin type 1 protein was increased at least 2-fold at 2, 5, and 15 weeks after cavopulmonary anastomosis (P =.005). Cavopulmonary anastomosis also increased angiotensin type 2 mRNA and protein expression at least 2-fold at 2 and 5 weeks (P =.02) after surgical intervention. At 15 weeks, expression of angiotensin type 2 mRNA and protein was unchanged from that seen in control animals. Immunolocalization in pulmonary tissue sections 2 weeks after cavopulmonary anastomosis revealed markedly enhanced staining of angiotensin II receptor type 1 in vascular smooth muscle and angiotensin II receptor type 2 in the endothelium of pulmonary arteries.
Rapid elevation in the expression of the type 1 and 2 angiotensin II receptors in the affected pulmonary vasculature after cavopulmonary anastomosis suggests their involvement in the pathologic vascular remodeling that occurs after cavopulmonary anastomosis.
[Show abstract][Hide abstract] ABSTRACT: Pulmonary arteriovenous malformations (PAVMs) are a cause of progressive cyanosis after cavopulmonary anastomosis in children with single ventricle physiology who are on the pathway leading to a Fontan procedure. Investigations into possible mechanisms for the etiology of PAVMs are ongoing and suggest that the liver might play a key regulatory role in the development of these lesions.
The Annals of Thoracic Surgery 12/2003; 76(5):1759-66. DOI:10.1016/S0003-4975(03)00450-8 · 3.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pulmonary arteriovenous fistulas are vascular malformations, which, by virtue of producing abnormal vascular connections proximal to the units of gas exchange, result in intrapulmonary right-to-left shunting. These malformations or fistulas reflect at least in part disordered angiogenesis, and less commonly recruitment and dilation of pre-existing vascular channels. Pulmonary arteriovenous fistulas occur in a number of diverse clinical settings. Such fistulas are a well-established feature of the Weber-Osler-Rendu complex, or hereditary haemorrhagic telangiectasia, an autosomal dominant vascular dysplasia characterized by mucocutaneous telangiectasis, epistaxis, gastrointestinal haemorrhage, and arteriovenous malformations in the lung, brain, liver and elsewhere. They are also seen in the patient with acute or chronic liver disease, disease that is usually but not invariably severe, or those with non-cirrhotic portal hypertension. They may occur as congenital malformations, single or diffuse, large or small in isolation, and when large or extensive enough may result in hypoxaemia, clinical cyanosis, and heart failure. Cerebral vascular accidents are also a well-known complication of this disorder. An extensive literature has accumulated with regard to the pulmonary arteriovenous fistulas seen in the setting of the Weber-Osler-Rendu complex, and there is considerable information on the genetics, basic biology, clinical findings, complications and therapeutic interventions of these malformations in the setting of this syndrome. These issues, however, are not the primary considerations of this review, although some aspects of this fascinating disorder will be discussed later. Rather the focus will be on pulmonary arteriovenous malformations that develop in the setting of cavopulmonary surgery, and their relationship to the pulmonary arteriovenous fistulas occurring in the hepatopulmonary syndrome. The complex tapestry of these overlapping and intersecting clinical observations will be unfolded in the light of their chronology.
Cardiology in the Young 09/2004; 14(4):417-37. DOI:10.1017/S1047951104004111 · 0.84 Impact Factor
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