Arteriovenous shunts in the peropheral pulmonary circulation in the human lung.

Tobin, Charles E.

doi:10.1136/thx.21.3.197

Cited by 103 publications

(70 citation statements)

References 18 publications

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“…Studies have demonstrated direct vascular anastomoses between pulmonary arteries and veins in many mammals including cats (9), dogs (9)(10)(11), and healthy humans (9,12,13). More recently, we have demonstrated that I-P arteriovenous pathways greater than 50 m are functional in fresh healthy ventilated and perfused isolated human lungs (14).…”

Section: What This Study Adds To the Fieldmentioning

confidence: 79%

“…In addition, previous work has shown that stroke patients have a higher prevalence of patent foramen ovale (38)(39)(40), and hereditary hemorrhagic telangiectasia patients are more susceptible to embolic stroke and neurologic symptoms (41), indicating that blood flow bypassing the pulmonary microcirculation may have important physiological relevance. Isolated lung work has shown that I-P arteriovenous shunts are up to 420 m in diameter in the dog (11), 390 m in the cat (9), and 200 m in the adult human (13). Further characterization of I-P shunts will determine whether exercise recruits similar large-diameter vessels that could have important neural and/or cardiovascular consequences.…”

Section: Shunt Consequencementioning

confidence: 99%

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Exercise-induced Arteriovenous Intrapulmonary Shunting in Dogs

Stickland

Lovering²,

Eldridge³

2007

Am J Respir Crit Care Med

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Rationale:We have previously shown, using contrast echocardiography, that intrapulmonary arteriovenous pathways are inducible in healthy humans during exercise; however, this technique does not allow for determination of arteriovenous vessel size or shunt magnitude. Objectives: The purpose of this study was to determine whether large-diameter (more than 25 m) intrapulmonary arteriovenous pathways are present in the dog, and whether exercise recruits these conduits. Methods: Through the right forelimb, 10.8 million 25-m stable isotope-labeled microspheres (BioPAL, Inc., Worcester, MA) were injected either at rest (n ϭ 8) or during high-intensity exercise (6-8 mph, 10-15% grade, n ϭ 6). Systemic arterial blood was continuously sampled during and for 3 minutes after injection. After euthanasia, tissue samples were obtained from the heart, liver, kidney, and skeletal muscle. In addition, 25-and 50-m microspheres were infused into four isolated dog lungs that were ventilated and perfused at constant pressures similar to exercise. Measurements and Main Results: Blood and tissue samples were commercially analyzed for the presence of microspheres. No microspheres were detected in the arterial blood or tissue samples from resting dogs. In contrast, five of six exercising dogs showed evidence of exercise-induced intrapulmonary arteriovenous shunting, as microspheres were detected in arterial blood and/or tissue. Furthermore, shunt magnitude was calculated to be 1.4 ؎ 0.8% of cardiac output (n ϭ 3). Evidence of intrapulmonary arteriovenous anastomoses was also found in three of four isolated lungs. Conclusions: Consistent with previous human findings, these data demonstrate that intrapulmonary arteriovenous pathways are functional in the dog and are recruited with exercise.Keywords: intrapulmonary arteriovenous anastomoses; shunt; pulmonary gas exchange; pulmonary circulationThe classic understanding of the normal pulmonary circulation is that all the blood leaving the right ventricle passes through the pulmonary microcirculation via capillaries before returning to the left side of the heart through the pulmonary venous circulation. Studies using saline contrast echocardiography in humans have demonstrated that exercise results in the transpulmonary passage of contrast bubbles, suggesting that large-diameter intrapulmonary (I-P) arteriovenous pathways are recruited with exercise (1-3). These findings are controversial in that they are in contrast with prior research, using inert gas and/or inspired 100% Previous studies, using contrast echocardiography, suggest that intrapulmonary shunts are recruited during exercise in health. However, the size of the contrast is unknown, and thus arteriovenous diameter is undefined. What This Study Adds to the FieldLarge-diameter intrapulmonary arteriovenous shunts are functional in healthy animals, and exercise recruits these vessels.oxygen (4)(5)(6)(7)(8), that has failed to detect substantial right-to-left physiological I-P shunt during exercise.Despite an absence of right-to-left I-P...

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Section: What This Study Adds To the Fieldmentioning

confidence: 79%

Section: Shunt Consequencementioning

confidence: 99%

Exercise-induced Arteriovenous Intrapulmonary Shunting in Dogs

Stickland

Lovering²,

Eldridge³

2007

Am J Respir Crit Care Med

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“…[2][3][4]8,9,[29][30] Although the size of IPAVs has never been directly determined in humans under physiologic conditions, data from isolated lung and intact animal studies suggest that these pathways are large (.200 mm) and are located early in the pulmonary vascular tree. 1,[31][32][33] Why Is This Case Relevant to the Clinician?…”

Section: Discussionmentioning

confidence: 99%

Transient Intrapulmonary Shunting in a Patient Treated With β2-Adrenergic Agonists for Status Asthmaticus

Bates¹,

Jacobson

Eldridge

2014

Pediatrics

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Intrapulmonary arteriovenous anastomoses (IPAVs) are largediameter pathways that directly connect the arterial and venous networks, bypassing the pulmonary capillaries. Ubiquitously present in healthy humans, these pathways are recruited in experimental conditions by exercise, hypoxia, and catecholamines and have been previously shown to be closed by hyperoxia. Whether they play a role in pulmonary pathophysiology is unknown. Here, we describe IPAV recruitment associated with hypoxemia and right-to-left shunt in a patient with status asthmaticus, treated with agonists of the B 2 -adrenergic pathway. Our observation of IPAVs in a pediatric patient, mechanically ventilated with 100% O 2 , suggests that these pathways are recruited in clinically important circumstances and challenges the notion that IPAVs are always closed by alveolar hyperoxia.

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“…[126][127][128] Physiologic demonstration of intrapulmonary shunt in fetal sheep has been shown by echocardiography, but shunting is less prominent in newborns. 129 Late persistence or enhancement of IAVCs has been previously reported in pathologic settings as neonatal heart disease requiring cavopulmonary shunt operations. More recently, the presence of striking IAVCs, or "shunt" vessels, has been confirmed by histology and 3-dimensional reconstruction methods in autopsy lung tissue from preterm infants who died with severe BPD and alveolar capillary dysplasia with misalignment of pulmonary veins (Figure 6).…”

Section: Pvd In Bpdmentioning

confidence: 99%

The Robyn Barst Memorial Lecture: Differences between the Fetal, Newborn, and Adult Pulmonary Circulations: Relevance for Age‐Specific Therapies (2013 Grover Conference Series)

et al. 2014

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Pulmonary arterial hypertension (PAH) contributes to poor outcomes in diverse diseases in newborns, infants, and children. Many aspects of pediatric PAH parallel the pathophysiology and disease courses observed in adult patients; however, critical maturational differences exist that contribute to distinct outcomes and therapeutic responses in children. In comparison with adult PAH, disruption of lung vascular growth and development, or angiogenesis, plays an especially prominent role in the pathobiology of pediatric PAH. In children, abnormalities of lung vascular development have consequences well beyond the adverse hemodynamic effects of PAH alone. The developing endothelium also plays critical roles in development of the distal airspace, establishing lung surface area for gas exchange and maintenance of lung structure throughout postnatal life through angiocrine signaling. Impaired functional and structural adaptations of the pulmonary circulation during the transition from fetal to postnatal life contribute significantly to poor outcomes in such disorders as persistent pulmonary hypertension of the newborn, congenital diaphragmatic hernia, bronchopulmonary dysplasia, Down syndrome, and forms of congenital heart disease. In addition, several studies support the hypothesis that early perinatal events that alter lung vascular growth or function may set the stage for increased susceptibility to PAH in adult patients ("fetal programming"). Thus, insights into basic mechanisms underlying unique features of the developing pulmonary circulation, especially as related to preservation of endothelial survival and function, may provide unique therapeutic windows and distinct strategies to improve short-and long-term outcomes of children with PAH.Keywords: pulmonary vascular development, angiogenesis, alveolarization, persistent pulmonary hypertension of the newborn, congenital diaphragmatic hernia, bronchopulmonary dysplasia, Down syndrome, pediatric pulmonary hypertension. Pulmonary arterial hypertension (PAH) is a devastating and progressive disease that is characterized by abnormalities of vascular tone and reactivity, vessel wall structure, growth, and thrombosis. 1 Mechanisms contributing to PAH and its progression are complex and remain incompletely understood. Insights into vascular biology over the past few decades have led to remarkable improvements in the clinical course, outcomes, and survival in adults with PAH, yet relatively few studies have been performed in children. As in adults, PAH contributes to poor outcomes in diverse cardiac, pulmonary, and systemic diseases in newborns, infants, and children (Table 1). 2 There is a clear need to define the natural history of pediatric PAH in diverse settings; to develop new strategies to identify at-risk patients early in their course; and to establish novel approaches to better diagnose, evaluate, and treat children with PAH. 3,4 Despite many similarities between pediatric and adult PAH, critical differences exist that currently limit our clinical appr...

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Arteriovenous shunts in the peropheral pulmonary circulation in the human lung.

Cited by 103 publications

References 18 publications

Exercise-induced Arteriovenous Intrapulmonary Shunting in Dogs

Exercise-induced Arteriovenous Intrapulmonary Shunting in Dogs

Transient Intrapulmonary Shunting in a Patient Treated With β2-Adrenergic Agonists for Status Asthmaticus

The Robyn Barst Memorial Lecture: Differences between the Fetal, Newborn, and Adult Pulmonary Circulations: Relevance for Age‐Specific Therapies (2013 Grover Conference Series)

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