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

Abstract

Rationale: Bronchopulmonary dysplasia (BPD) is the chronic lung disease of infancy that occurs in premature infants after oxygen and ventilator therapy for acute respiratory disease at birth. Despite improvement in current therapies, the clinical course of infants with BPD is often characterized by marked hypoxemia that can become refractory to therapy. Preacinar anatomic and functional communications between systemic and pulmonary vascular systems has been established in fetal lungs, but whether increased intrapulmonary anastomotic vessels or their failure to regress after birth contributes to hypoxemia in preterm infants with BPD is unknown.Objectives: We sought to find histologic evidence of intrapulmonary anastomotic vessels in lungs of patients who died of severe BPD. Methods:We collected lung tissues from fatal BPD cases and performed histology, immunohistochemistry, and high-precision three-dimensional reconstruction techniques. Measurements and Main Results:We report histologic evidence of intrapulmonary vessels that bridge pulmonary arteries and veins in the distal lungs of infants dying with severe BPD. These prominent vessels appear similar to "misaligned pulmonary veins" described in the lethal form of congenital lung disorder, alveolar capillary dysplasia. Conclusions:We found striking histological evidence of precapillary arteriovenous anastomotic vessels in the lungs of infants with severe bronchopulmonary dysplasia. We propose that persistence or expansion of these vessels after premature birth provides the anatomic basis for intrapulmonary shunt and hypoxemia in neonates with severe bronchopulmonary dysplasia and may play a significant role in the morbidity and mortality of BPD.Keywords: intrapulmonary shunt; bronchopulmonary dysplasia; pulmonary circulation; vascular development

Histologic Evidence of Intrapulmonary Bronchopulmonary Anastomotic Pathways in Neonates with Meconium Aspiration Syndrome

“…[3][4][5][6] In these infants, we found prominent anastomotic connections between bronchial arteries and pulmonary arteries as well as markedly dilated bronchial and pulmonary veins. These findings suggest the presence of intrapulmonary shunt vessels that may also contribute to hypoxia.…”

“…Histologic evidence of shunt vessels were not found in infants who died from nonrespiratory causes, as we have previously shown (Figure, D). 3 …”

Early Pulmonary Vascular Disease in Preterm Infants at Risk for Bronchopulmonary Dysplasia

“…The pulmonary circulation in BPD is characterized by abnormal growth, including decreased vascular branching, an altered pattern of vascular distribution within the interstitium, and persistent precapillary arteriovenous anastomotic vessels (3,(10)(11)(12)(13)(14). Although the pathogenesis of BPD is complex and multifactorial (15), preclinical studies have shown that early disruption of angiogenesis in the developing lung impairs alveolarization and causes sustained abnormalities of lung structure that mimic clinical BPD (16)(17)(18).…”

Pulmonary Hypertension in Preterm Infants with Bronchopulmonary Dysplasia

“…69 IAAV are small connecting vessels that shunt deoxygenated blood into the pulmonary venous circulation and thus prevent gas exchange at the alveolar-capillary interface (Fig. 2).…”