Morphological Studies of Pulmonary Arteriovenous Shunting in a Lamb Model of Superior Cavopulmonary Anastomosis

Abstract

We sought to identify and characterize the abnormal vascular structures responsible for pulmonary arteriovenous shunting following the Glenn cavopulmonary shunt. Superior cavopulmonary shunt is commonly performed as part of the staged pathway to total cavopulmonary shunt to treat univentricular forms of congenital heart disease, however, clinically significant pulmonary arteriovenous malformations develop in some patients after the procedure. The causes of pulmonary arteriovenous malformations and other pulmonary vascular changes that occur after cavopulmonary shunt are not known. Using a juvenile lamb model of superior cavopulmonary anastomosis that reliably produces pulmonary arteriovenous malformations, we performed echocardiography and morphological analyses to determine the anatomic site of shunting and to identify the vascular structures involved. Pulmonary arteriovenous shunting was identified by contrast echocardiography in all surviving animals (n = 40) following superior cavopulmonary anastomosis. Pulmonary vascular corrosion casts revealed abnormal tortuous vessels joining pulmonary arteries and veins in cavopulmonary shunt animals but not control animals. In conclusion, unusual channels that bridged pulmonary arteries and veins were identified. These may represent the vascular structures responsible NIH Public Access KeywordsHeart defects; Congenital pulmonary circulation; Arteriovenous malformationThe classic Glenn surgical superior cavopulmonary anastomosis (CPA) is commonly performed as part of the staged Fontan pathway to treat univentricular forms of congenital heart disease [6,7]. Up to 60% of these patients develop pulmonary arteriovenous shunting (PAVS), which may lead to progressive and clinically significant hypoxia [1][2][3]11]. Although PAVS is believed to occur via pulmonary arteriovenous malformations (PAVMs) that develop following creation of a Glenn shunt, the vascular structures responsible for PAVS have not been clearly characterized. It is commonly believed that PAVMs develop because of the absence of a putative hepatic venous 'factor' in the pulmonary circulation of these patients [9,15,17]. Identification and morphologic analysis of the structural components responsible for PAVMs may provide a better understanding of abnormal vascular developmental processes in these patients and facilitate isolation of putative circulating etiological substances. Using a juvenile lamb model that reliably produces pulmonary arteriovenous malformations, we performed echocardiographic, angiographic, and morphologic analyses to identify and characterize the vascular structures involved in PAVS following the Glenn shunt. Materials and MethodsThese studies were performed in compliance with animal welfare regulations of the University of California-San Francisco and USDA guidelines. Furthermore, these studies conformed to the "Position of the American Heart Association on Research Animal Use," adopted by the American Heart Association on November 11, 1984, and were approved by the University o...

Embryology and Anatomy of Intrapulmonary Shunts

“…The purpose of these channels during fetal development has not been clearly established, but they may play a role in regulating pulmonary vascular resistance and pulmonary blood flow by acting as functional pressure relief valve to protect the thin‐walled perialveolar vasculature. Fetal pulmonary arteriovenous shunting disappears during early neonatal life and is not present in healthy adolescent or adult sheep . The time course of PAVS resolution parallels that of other dynamic changes occurring in the pulmonary circulation such as closure of the ductus arteriosus and falling pulmonary vascular resistance, suggesting that these processes may be mediated by similar mechanical and biochemical factors.…”

“…The walls in this region of the supernumerary artery contain dynamic musculoelastic cushions, which appear to act as sphincters that regulate the flow of blood into supernumerary vessels. While a direct relationship between sphincter‐like cushions embedded in supernumerary vessels and inducible pulmonary arteriovenous shunting has not been established, the potential for these structures to modulate supernumerary vessel blood flow and thereby divert blood away from perialveolar capillary networks suggests that they may play a role in inducible pulmonary arteriovenous shunting …”

“…Animal models of the Glenn superior cavopulmonary anastomosis have provided important insights into the vascular morphological changes responsible for induced pulmonary arteriovenous shunting . Using calibrated microspheres and corrosion casting techniques, numerous central pulmonary arteriovenous malformations are identifiable within several weeks of the Glenn procedure.…”

Pulmonary arteriovenous malformations after the superior cavopulmonary shunt: mechanisms and clinical implications

“…[24] Morphologic studies of PAVMs in the lungs of lambs following a Glenn shunt using novel vascular corrosion casts demonstrated multiple abnormal tortuous vessels, a minimum of 15 μm in size, connecting the pulmonary arteries to the pulmonary veins, and bypassing the pulmonary alveolar beds . [25] .…”

Pulmonary arteriovenous malformation in two adult alpacas (Vicugna pacos)

“…Vital parameters were normal other than mild dehydration, and careful thoracic and tracheal auscultation revealed no signs of respiratory distress at that time. Blood was drawn for standard hematologic and serum chemistry panels, revealing a mild, nonregenerative anemia (9.91 × 10 6 interval: 13-28 mg/dl). The next day, the animal sustained a spontaneous, severe episode of hemorrhage from the mouth and nostrils accompanied by dyspnea, followed by death.…”