The biological “scrabble” of pulmonary arteriovenous malformations: considerations in the setting of cavopulmonary surgery

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.

Histologic Evidence of Intrapulmonary Anastomoses by Three-Dimensional Reconstruction in Severe Bronchopulmonary Dysplasia

“…Furthermore, IAAV are present in pathologic conditions in adult lungs after cavopulmonary shunt operations (30) and with hepatopulmonary syndrome (31). Recruitment of IAAV leads to shunting of blood away from distal airspace, thereby decreasing gas exchange and causing systemic hypoxemia (as illustrated in Figure 4).…”

Endostatin, an Inhibitor of Angiogenesis, Decreases After Bidirectional Superior Cavopulmonary Anastamosis

“…It has been recognized for the past 15 years that diversion of hepatic venous effluent away from the lung or impaired hepatic function plays a significant role in the pathogenesis of PAVMs [19]. Furthermore, structural similarities exist between PAVMs developing after bidirectional Glenn and the hepatopulmonary syndrome (HPS) from biliary and liver disease [7]. Specifically, there are dilated precapillary and capillary pulmonary blood vessels, increased microvessel density, and animal model data consistent with abnormal vascular remodeling [20, 23].…”

Constitutively active endothelial Notch4 causes lung arteriovenous shunts in mice

“…LUNG ARTERIOVENOUS (AV) shunting and malformations (AVMs) can occur in a variety of clinical settings, including hepatopulmonary syndrome (32), congenital heart disease (resulting from cavopulmonary anastomosis) (2,38), hereditary hemorrhagic teleangiectasia (HHT) (8), and as isolated lesions (11). Approximately one-third of patients with HHT (incidence 1 in 10,000) (8) or cirrhosis (incidence 5% of the general population) (12,34) have been estimated to harbor lung AV shunts or malformations.…”