Abstract 14845: Pulmonary Vascular Response to Inhaled Nitric Oxide is Related to the Mitochondrial Enzyme Carbamyl-Phosphate Synthetase I T1405N Polymorphism in Pediatric Patients With Congenital Cardiac Communications

Background and objectiveAssessment of pulmonary vasoreactivity is important in congenital heart disease with pulmonary hypertension (CHD-PHT). It may be altered in conditions such as Down syndrome and increasing age. We analyzed how pulmonary vascular response to inhaled nitric oxide (NO) might be influenced by the mitochondrial enzyme carbamyl-phosphate synthetase I (CPSI) T1405N polymorphism which has been associated with neonatal and postoperative PHT. In contrast to the CC T1405N genotype (threonine variant), the presence of at least one copy of the A allele (asparagine variant) has been shown to be protective against PHT.Patients and MethodsTwenty-seven CHD-PHT patients were enrolled (ages, 4 - 37 months); 19 of them had Down syndrome. Pulmonary and systemic vascular resistances (PVR and SVR) were determined during cardiac catheterization Parameters were recorded at baseline and during NO inhalation (40 ppm, 10 min.). CPSI T1405N polymorphism was investigated by polymerase chain reaction-coupled high-resolution melting analysis.ResultsIn the study population, CC (n=14) and AC (n=13) CPSI genotypes were identified. These groups did not differ in terms of age (respectively, 15 [10-22] mos. and 11 [8-16] mos., geometric mean with 95% CI, p=0.308) or prevalence of Down syndrome (respectively, 71% and 69%, p=0.901). Baseline PVR was elevated in both groups and decreased in response to NO (6.4 [4.4-9.4] U x m to 4.8 [2.9-7.9] U x m in patients with the CC CPSI genotype, p=0.002 and 4.5 [3.4-5.9] U x m to 2.7 [1.9-3.7] U x m in subjects with the AC genotype, p