Fecal α1-Antitrypsin Concentrations as a Measure of Enteric Protein Loss After Modified Fontan Operations

Fujii, Tohru; Shimizu, Toshiaki; Takahashi, Ken; Kishiro, Masahiko; Ohkubo, Mataichi; Akimoto, Katsumi; Yamashiro, Yuichiro

doi:10.1097/00005176-200311000-00014

Cited by 31 publications

(25 citation statements)

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“…To mimic venous hypertension in vitro, we established a tissue culture model of PLE using modified Ussing chambers that allow us to apply hydrostatic pressure to the basolateral surface of intestinal epithelial cells. The Fontan procedure elevates right atrial pressure by several mm Hg (mean, 10.9 mm Hg; normal, Ͻ3-5 mm Hg) (12), but the exact pressure in subepithelial capillaries is hard to assess. In our in vitro model, an increased hydrostatic pressure in the magnitude of a few mm H 2 O ( 1 ⁄ 13 mm Hg) already causes significant protein leakage (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Venous pressure is elevated immediately after the Fontan procedure, and post-Fontan patients already show a subtle increase in enteric protein loss determined by fecal ␣1-antitrypsin concentrations (12). Heart transplantation decreases pressure and normalizes protein loss (28), indicating a direct correlation between increased pressure and protein leakage.…”

Section: Discussionmentioning

confidence: 99%

“…Although the surgery vastly improves survival, it often elevates central venous pressure (11). Venous hypertension in post-Fontan patients is thought to be associated with intestinal protein leakage with the increased pressure from the basolateral side pressing plasma proteins into the intestinal lumen (11,12). Because venous pressure increases immediately after the intervention and remains elevated for the rest of the patient's life, there is no good explanation why PLE develops in only 3-10% of the patients months to years after the surgery (3,4).…”

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confidence: 99%

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Heparan Sulfate Plays a Central Role in a Dynamic in Vitro Model of Protein-losing Enteropathy

Bode

Murch

Freeze

2006

Journal of Biological Chemistry

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Protein-losing enteropathy (PLE), the loss of plasma proteins through the intestine, is a symptom in ostensibly unrelated diseases. Emerging commonalities indicate that genetic insufficiencies predispose for PLE and environmental insults, e.g. viral infections and inflammation, trigger PLE onset. The specific loss of heparan sulfate (HS) from the basolateral surface of intestinal epithelial cells only during episodes of PLE suggests a possible mechanistic link. In the first tissue culture model of PLE using a monolayer of intestinal epithelial HT29 cells, we proved that HS loss directly causes protein leakage and amplifies the effects of the proinflammatory cytokine tumor necrosis factor ␣ (TNF␣). Here, we extend our in vitro model to assess the individual and combined effects of HS loss, interferon ␥ (IFN␥), TNF␣, and increased pressure, and find that HS plays a central role in the patho-mechanisms underlying PLE. Increased pressure, mimicking venous hypertension seen in postFontan PLE patients, substantially increased protein leakage, but HS loss, IFN␥, or TNF␣ alone had only minor effects. However, IFN␥ up-regulated TNFR1 expression and amplified TNF␣-induced protein leakage. IFN␥ and TNF␣ compromised the integrity of the HT29 monolayer and made it more susceptible to increased pressure. HS loss itself compromises the integrity of the monolayer, amplifying the effects of pressure, but also amplifies the effects of both cytokines. In the absence of HS a combination of increased pressure, IFN␥, and TNF␣ caused maximum protein leakage. Soluble heparin fully compensated for HS loss, providing a reasonable explanation for patient favorable response to heparin therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Heparan Sulfate Plays a Central Role in a Dynamic in Vitro Model of Protein-losing Enteropathy

Bode

Murch

Freeze

2006

Journal of Biological Chemistry

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“…As suggested by Fuji 64 , in 2003, the fecal protein loss precedes hypoproteinemia. One wonders whether these patients would have a better outcome if treated before the appearance of the full-blown syndrome.…”

Section: Preventionmentioning

confidence: 89%

Enteropatia perdedora de proteínas após cirurgia de Fontan

Amaral

Atik

2006

Arq. Bras. Cardiol.

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“…Much remains to be proven in this respect, but it is necessary to always bear in mind the Fontan operation is a palliative intervention and has a series of inconveniences such as the complications already mentioned, as well as the demonstration of elevation of α-1-antitrypsin even in the absence of hipoproteinemia 17 , the subclinical coagulation disorders 18 , and the elevation of systemic venous pressure itself, that place the outcome of these patients at risk.…”

Section: At Instituto Do Coração Da Faculdade De Medicina Damentioning

confidence: 99%

Operação de Fontan: reflexões da evolução e perspectivas atuais

Atik¹

2006

Arq. Bras. Cardiol.

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Fontan, congenital heart diseases, surgery.As the Fontan operation 1 became the most frequently performed surgery in Pediatric Cardiology for the functional correction of many congenital heart diseases with singleventricle physiology, it started to be considered in relation to the most suitable maneuvers to minimize the complications that still challenge its management in the long term.Although the incidence of such complications has decreased mainly as from 1988 with the introduction of the total cavopulmonary technique 2 , we can still observe the occurrence of morbidity elements whose rates are disturbing and affect the evolution of this method.Because of the dynamics imposed on the new anatomic situation with the cavopulmonary connection which eliminates the pulsatile function of the right ventricle and establishes the slow venous flow through the venae cavae to the pulmonary arterial tree, the occurrence of complications resulting from congestive, electrical and thromboembolic aspects is thus facilitated.The congestive aspects are characterized by increased venous pressure, hepatomegaly, protein-losing enteropathy due to lymphangiectasia, lower-extremity edema, and ascitis.The electrical aspects concern both the decrease in sinus automatism and supraventricular arrhythmias such as extrasystoles, fibrillation, and paroxysmal tachycardias.The thromboembolic aspects, which start in the venous system and in venous-arterial junctions and conduit connections, are also related to the occurrence of several coagulation disorders caused by factors resulting from liver congestion.Pathogenic factors of these adverse elements are related to preoperative anatomic and functional aspects and that is why a more accurate analysis of these aspects is mandatory at the moment of the surgical procedure.In this setting, it is well timed to recall and mention the factors considered optimal for the surgical indication, which are mainly: preserved ventricular function close to normal, adequate pulmonary arterial tree with mean pressures below 15 mmHg and pulmonary resistance lower than 2U Wood, and also the presence of sinus rhythm responsive to stimuli 3 . Absence of atrioventricular and aortic regurgitation, of fistulae and systemic-pulmonary anastomotic vessels, in addition to myocardial hypertrophy are also included.These deleterious factors are effectively responsible for the mortality that occurs throughout time and which ranges, according to the expertise of each medical center, from 15 to 30% 15 years after the surgical procedure 3 . That is where death results from, mainly related to heart failure, arrhythmias, thromboembolism, and to protein-losing syndrome.Among the complications, those with the highest prevalence and repercussion are heart failure and arrhythmias, mainly in atriopulmonary 4-6 techniques, but also in cavopulmonary 7 procedures when performed in adulthood. These complications are less frequent in cavopulmonary connections with extracardiac conduits 8 than in intra-atrial lateral tunnel 7,9 . Other complica...

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Fecal α1-Antitrypsin Concentrations as a Measure of Enteric Protein Loss After Modified Fontan Operations

Cited by 31 publications

References 10 publications

Heparan Sulfate Plays a Central Role in a Dynamic in Vitro Model of Protein-losing Enteropathy

Heparan Sulfate Plays a Central Role in a Dynamic in Vitro Model of Protein-losing Enteropathy

Enteropatia perdedora de proteínas após cirurgia de Fontan

Operação de Fontan: reflexões da evolução e perspectivas atuais

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