Exercise-induced intrapulmonary arteriovenous shunting in healthy humans

Eldridge, Marlowe W.; Dempsey, Jerome A.; Haverkamp, Hans Christian; Lovering, Andrew T.; Hokanson, John S.

doi:10.1152/japplphysiol.00137.2004

Cited by 205 publications

(266 citation statements)

References 63 publications

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“…No dog was found to have an intracardiac shunt during postmortem examination, which, combined with the isolated lung data demonstrating 25-to 50-m microspheres in the pulmonary venous outflow, indicates that the conduits allowing microspheres to bypass the pulmonary microcirculation in the intact animal were I-P arteriovenous pathways, and not of cardiac origin. Consistent with previous human exercise studies (1)(2)(3), these data confirm that large-diameter (Ͼ 25 m) I-P arteriovenous pathways are recruited with exercise.…”

Section: Discussionsupporting

confidence: 90%

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: Discussionsupporting

confidence: 90%

Exercise-induced Arteriovenous Intrapulmonary Shunting in Dogs

Stickland

Lovering²,

Eldridge³

2007

Am J Respir Crit Care Med

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“…Small, poorly perfused "supernumerary" arteries have been identified in the normal pulmonary circulation and are believed to function as recruitable sources of pulmonary blood flow when oxygenation demands are high [5,16]. Recently, exercise-induced PAVS has been described in otherwise normal, healthy humans [4]. Taken together, these findings support our belief that PAVS associated with CPA or other processes affecting the developing pulmonary circulation may reflect regression of pulmonary vascular remodeling to an earlier (fetal) developmental state.…”

mentioning

confidence: 54%

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

McMullan¹,

Reddy

Gottliebson

et al. 2007

Pediatr Cardiol

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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...

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“…[4][5][6][7] While these physiological transpulmonary arteriovenous pathways are subclinical in most instances, they have potential to open in up to 90% of individuals during hyperdynamic situations such as exercise. [8][9][10] A recent review of pulmonary pathways and mechanisms pertaining to their autoregulation highlights the interest and importance of this subject. 11 Neuroanesthesiologists are well aware of the multiple pathways for paradoxical air embolism (PAE) to occur.…”

Section: Résumémentioning

confidence: 99%