Effect of cardiopulmonary bypass on urea cycle intermediates and nitric oxide levels after congenital heart surgery

Barr, Frederick E.; Beverley, H.L. Kelso; VanHook, Kristin; Cermak, Emma; Christian, Karla G.; Drinkwater, Davis C.; Dyer, Karrie L.; Raggio, Noel T.; Moore, Jason H.; Christman, Brian W.; Summar, Marshall

doi:10.1067/mpd.2003.mpd0311

Cited by 48 publications

(44 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a previous study of infants undergoing congenital heart surgery, we found significantly decreased postoperative levels of arginine, citrulline (a urea cycle intermediate and precursor of arginine) and nitric oxide metabolites (Barr, 2003). In that study, arginine levels fell by more than 50% and did not recover until 48 hours following surgery (Barr, 2003).…”

Section: Discussionmentioning

confidence: 73%

“…In that study, arginine levels fell by more than 50% and did not recover until 48 hours following surgery (Barr, 2003). In a related study, we demonstrated the effectiveness of oral citrulline in preserving preoperative levels of arginine and decreasing the risk of postoperative pulmonary hypertension in a similar population of children undergoing repair of congenital heart defects (Smith et al, 2006).…”

Section: Discussionmentioning

confidence: 85%

“…Endothelial cells generate NO from arginine, a precursor amino acid supplied by the urea cycle (Moncada and Higgs, 1993). We have previously demonstrated that infants undergoing surgical repair of congenital heart defects have significantly decreased serum arginine levels in the immediate postoperative period (Barr et al, 2003). This decrease in availability of a key substrate for NO following cardio-pulmonary bypass may increase the risk of postoperative pulmonary hypertension (Barr et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: A validated genetic association study

et al. 2007

Self Cite

View full text Add to dashboard Cite

Increased pulmonary artery pressure (PAP) can complicate the postoperative care of children undergoing surgical repair of congenital heart defects. Endogenous NO regulates PAP and is derived from arginine supplied by the urea cycle. The rate-limiting step in the urea cycle is catalyzed by a mitochondrial enzyme, carbamoyl-phosphate synthetase I (CPSI). A well-characterized polymorphism in the gene encoding CPSI (T1405N) has previously been implicated in neonatal pulmonary hypertension. A consecutive modeling cohort of children (N=131) with congenital heart defects requiring surgery was prospectively evaluated to determine key factors associated with increased postoperative PAP, defined as a mean PAP > 20mmHg for at least one hour during the 48 hours following surgery measured by an indwelling pulmonary artery catheter. Multiple Dimensionality Reduction (MDR) was used to both internally validate observations and develop optimal two-variable through five-variable models that were tested prospectively in a validation cohort (N= 41). Unconditional logistic regression analysis of the modeling cohort revealed that age (OR= 0.92, p=0.01), CPSI T1405N genotype (AC vs. AA: OR=4.08, p=0.04, CC vs. AA: OR=5.96, p=0.01), and Down syndrome (OR=5.25, p=0.04) were independent predictors of this complex phenotype. MDR predicted that the best two-variable model consisted of age and CPSI T1405N genotype (p<0.001). This two-variable model correctly predicted 73% of the outcomes from the validation cohort. A five-variable model that added race, gender and Down's syndrome was not significantly better than the two-variable model. In conclusion, the CPSI T1405N genotype appears to be an important new factor in predicting susceptibility to increased PAP following surgical repair of congenital cardiac defects in children.

show abstract

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: A validated genetic association study

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…25 Consistent with these findings, the CPSI T1405N SNP appears to play a similar role in other phenotypes characterized by oxidant stress and vascular injury. 21,26,27 Nitric oxide is also a regulator of intracellular iron metabolism during inflammation. 28 Iron augments oxidant liver injury.…”

mentioning

confidence: 99%

Genomic screening and complications of hematopoietic stem cell transplantation: has the time come?

Kallianpur

2004

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:The occurrence of toxic complications following hematopoietic stem cell transplantation (HSCT) is highly variable and dependent on a multitude of host, donor, and treatment factors. The increasingly broad indications for HSCT and the need to provide this treatment option to older and/or more debilitated patients emphasizes the importance of refining our methods of predicting and ameliorating these toxicities. Late complications (occurring after day 100) also pose a threat to quality of life after HSCT. Genetic polymorphisms in key molecular pathways in the host are likely to contribute significantly to the observed variability in the development HSCT-associated complications. Hepatic veno-occlusive disease and acute lung injury, two of the most serious organ toxicities that occur, represent useful paradigms for the identification of genetic polymorphisms in enzyme systems that modulate local and systemic responses to oxidant stress during transplant conditioning therapy. Ongoing studies in this area are providing clues to the prevention of adverse clinical outcomes based on the genetic milieu. This review of studies in HSCT that explore genetic risk factors for transplant complications indicates that significant progress is being made in this rapidly evolving area. However, further large-scale clinical and translational studies are needed before genomic screening can be widely used to individualize treatment. Bone Marrow Transplantation (2005) Clinicians are continually challenged by the need to predict the responses of individual patients to potentially toxic treatments. The increasing promise of cure for patients who undergo hematopoietic stem cell transplantation (HSCT) for life-threatening disorders is overshadowed by the very real threat of short-term, often fatal, complications resulting from the transplant regimen and graft-versushost disease (GVHD). However, significant variation is observed between similarly treated individuals in the development of complications. It is an appealing concept, therefore, and one to which many clinicians now subscribe, that a significant portion of this variability has a genetic basis. Identifying important genetic variables will allow for better prediction of HSCT-related outcomes, and in the process of identifying these susceptibilities, it may also be possible to gain sufficient knowledge of the underlying pathophysiology of these toxicities to develop targeted interventions.This review will focus on genomic screening of the host for the prediction of specific complications, touching briefly on selected donor factors. Other rapidly evolving areas that are not covered include molecular genetic testing to predict graft failure and disease relapse after HSCT. The role of clinical and biochemical risk factors in the pre-transplant evaluation of HSCT candidates has also been reviewed recently in this journal. 1 Importance of context-dependent genetic effectsThe study of uncommon disease-associated mutations has been invaluable to our understanding of basic pathophy...

show abstract

“…128 L-arginine and citrulline levels are decreased in neonates with PPHN, in adults and children with PH related to sickle-cell disease, and in infants and children after cardiac surgery. [129][130][131][132] In a small study, 5 neonates with PPHN received a single dose of intravenous L-arginine, which decreased the oxygenation index and increased oxygen saturation. 133 In another study, 10 patients (age range 13-63 years) with sickle-cell disease were treated with oral L-arginine for 5 days and had a 15% decrease in estimated PAP.…”

Section: Nitric Oxide-cgmp Cascade: Inhaled Nitric Oxidementioning

confidence: 99%

Advances in the Management of Pediatric Pulmonary Hypertension

2011

View full text Add to dashboard Cite

Pulmonary hypertension is a rare disease in neonates, infants, and children, and is associated with substantial morbidity and mortality. An adequate understanding of the controlling pathophysiologic mechanisms is lacking. Moreover, a minority of research is focused specifically on neonatal and pediatric populations. Although therapeutic options have increased over the past several decades, they remain limited. In advanced pulmonary hypertension, progressive pulmonary vascular functional and structural changes ultimately cause increased pulmonary vascular impedance, rightventricular failure, and death. Management includes the prevention and/or treatment of active pulmonary vasoconstriction, the support of right-ventricle function, treatment of the underlying disease (if possible), and the promotion of regressive remodeling of structural pulmonary vascular changes. Most currently available therapies augment or inhibit factors, or mediators of their downstream signaling cascades, that originate in the pulmonary vascular endothelium. These pathways include nitric-oxide/cyclic guanosine monophosphate (cGMP), prostacyclin, and endothelin-1. The ability to reverse advanced structural changes remains an as yet unattained goal. This paper reviews the epidemiology, pathophysiology, current treatments, and emerging therapies related to neonatal and pediatric pulmonary hypertension.

show abstract

Effect of cardiopulmonary bypass on urea cycle intermediates and nitric oxide levels after congenital heart surgery

Cited by 48 publications

References 24 publications

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: A validated genetic association study

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: A validated genetic association study

Genomic screening and complications of hematopoietic stem cell transplantation: has the time come?

Advances in the Management of Pediatric Pulmonary Hypertension

Contact Info

Product

Resources

About