Nitric oxide precursors and congenital heart surgery: A randomized controlled trial of oral citrulline

Smith, Heidi; Canter, Jeffrey A.; Christian, Karla G.; Drinkwater, Davis C.; Scholl, Frank G.; Christman, Brian W.; Rice, Geraldine D.; Barr, Frederick E.; Summar, Marshall

doi:10.1016/j.jtcvs.2006.02.012

Cited by 92 publications

(77 citation statements)

References 18 publications

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“…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: 82%

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

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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.

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Section: Discussionmentioning

confidence: 82%

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

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“…This may be demonstrated by increased pulmonary vascular resistance and episodes of pulmonary hypertension [1][2][3]. When repair is carried out, surgery and cardiopulmonary bypass can further exacerbate pulmonary endothelial dysfunction; this occurs by several mechanisms including cytokine activation and ischaemiareperfusion injury [1].…”

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confidence: 99%

“…Pulmonary endothelial dysfunction can be defined as Ó 2011 The Authors a failure of the pulmonary endothelium to produce adequate amounts of NO, with a loss of vascular homeostasis [2,3]. Nitrous oxide acts through a secondary messenger, intracellular cyclic guanosine monophosphate (cGMP), to vasodilate pulmonary blood vessels, and is finally oxidised to form nitrate and nitrite [2,4].…”

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confidence: 99%

Pre‐operative sildenafil and pulmonary endothelial‐related complications following cardiopulmonary bypass: a randomised trial in children undergoing cardiac surgery*

et al. 2011

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SummaryIn a randomised trial, we compared the effects of oral sildenafil (0.5 mg.kg )1 ) and placebo, , respectively; p = 0.002; right ventricle 6.93 (1.47) vs 8.09 (2.25) cm.s )1 , respectively; p < 0.001) were significantly reduced in the sildenafil group. In this trial, pre-operative sildenafil did not affect postoperative pulmonary vascular resistance. There was, however, a negative impact on ventricular function and oxygenation.

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“…136 Citrulline level above 37 mol/L appeared to protect against the development of postoperative PH.…”

Section: Nitric Oxide-cgmp Cascade: Inhaled Nitric Oxidementioning

confidence: 89%

Advances in the Management of Pediatric Pulmonary Hypertension

2011

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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.

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Nitric oxide precursors and congenital heart surgery: A randomized controlled trial of oral citrulline

Cited by 92 publications

References 18 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

Pre‐operative sildenafil and pulmonary endothelial‐related complications following cardiopulmonary bypass: a randomised trial in children undergoing cardiac surgery*

Advances in the Management of Pediatric Pulmonary Hypertension

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