Efficacy of citrulline supplementation to decrease the risk of pulmonary hypertension after congenital heart disease surgery. A local experience.

Authors

  • PhD. 1 Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas (CEMECO). Córdoba, Argentina. 2 Consejo Nacional de Investigación Científica y Técnica (CONICET), Ministerio de Ciencia, Tecnología e Innovación. Argentina.
  • Carola L Grosso Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas (CEMECO). Córdoba, Argentina. 3 Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Clínica Pediátrica. Córdoba, Argentina.
  • Margot Tablada Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Cátedra de Estadística y Biometría. Córdoba, Argentina.
  • Marcelo Cabrera Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Servicio de Cardiología. Córdoba, Argentina.
  • Raquel Dodelson de Kremer Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas (CEMECO). Córdoba, Argentina. 3 Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Clínica Pediátrica. Córdoba, Argentina.
  • Ernesto Juaneda Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Servicio de Cardiología. Córdoba, Argentina.
  • Laura E Laróvere Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas (CEMECO). Córdoba, Argentina. 2 Consejo Nacional de Investigación Científica y Técnica (CONICET), Ministerio de Ciencia, Tecnología e Innovación. Argentina. 3 Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Clínica Pediátrica. Córdoba, Argentina.

DOI:

https://doi.org/10.31053/1853.0605.v77.n4.27936

Keywords:

citrulline, pulmonary hypertension, nitric oxide, cardiology

Abstract

Pulmonary hypertension (PH) is a major cause of morbi-mortality among patients with congenital heart disease (CHD) and also a potentially severe complication after surgical repair. Oral citrulline, a precursor to NO synthesis, is safe and efficacious for decreasing the risk of postoperative PH.

Objective: The aim of the present study was to investigate in pediatric patients the changes of plasma citrulline, arginine, homocysteine and nitric oxide (NO) metabolites and pulmonary artery pressures (PAP) pre-post cardiac surgery in order to describe our population status with regard to the risk of pulmonary hypertension and look for potential biomarkers for early detection and treatment.

Main results/Discussion: 16 Argentine pediatric patients with CHD undergoing cardiopulmonary bypass were randomized in two groups: (A) with and (B) without perioperative citrulline supplementation. We found that plasma citrulline median levels before surgery were lower in both groups respect to referential values, probably due to the poor nutritional status of our patients; only group A surpassed post-surgery the minimum recommended level to avoid PH. Furthermore, none of the patients in group A showed mean PAP higher than 20 mmHg, whereas in group B, 67% of the measurements were ≥ than the reference level.

Conclusions: We reaffirm that citrulline supplementation it is effective in reducing postoperative pulmonary hypertension and biomarkers could evidence patient status as a translational medicine application.

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Author Biographies

PhD., 1 Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas (CEMECO). Córdoba, Argentina. 2 Consejo Nacional de Investigación Científica y Técnica (CONICET), Ministerio de Ciencia, Tecnología e Innovación. Argentina.

Graduate in Genetics from the National University of Misiones and Dr. in Biological Sciences, National University of Río Cuarto.

Position: Postdoctoral Fellow of the National Council for Scientific and Technical Research (CONICET) at the Research Center for Clinical Biochemistry and Immunology (CIBICI) and the Center for the Study of Inherited Metabolic Diseases (CEMECO), Children's Hospital of Córdoba.

Research interests in inborn errors of metabolism, urea cycle defects and medical genetics.

Training Research Program at the Urea Cycle Research Laboratory, Children's National Medical Center, Washington DC, United States.

Publications: 4 articles published in peer-reviewed scientific journals in the field of inborn errors of metabolism.

Societies / Editorial committees: Member of the Latin American Society of Birth Errors of Metabolism and Neonatal Screening. Ad hoc Evaluator Journal of Pediatric Genetics, International Journal of Rare Diseases and Disorders, and Journal of Inherited Metabolic Diseases.

Carola L Grosso, Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas (CEMECO). Córdoba, Argentina. 3 Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Clínica Pediátrica. Córdoba, Argentina.

Biologist and PhD in Chemical Sciences, degrees awarded by the National University of Cordoba.

Position: Center for the Study of Inherited Metabolic Diseases (CEMECO), Hospital de Niños de Córdoba and Assistant Professor of Pediatrics, School of Medicine, National University of Cordoba, since 1995.

Research Interests in sulphur aminoacid disorders.

Training Research Program in CEDEM-UAM, Madrid, Spain.

Publications in international journals with reference: 7, in the area of ​​genetic metabolic diseases.

Societies / Editorial Committees: Member of the Scientific Committee of the Latin American Society of Innate Errors of Metabolism and Neonatal Research.

Director / Co-director / Researcher of Projects subsidized by Secretariat of Science and Technology (SECyT) of the National University of Córdoba and FONCyT of the National Agency for Scientific and Technological Promotion, Argentina

 

Margot Tablada, Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Cátedra de Estadística y Biometría. Córdoba, Argentina.

Agricultural Engineer from the Faculty of Agricultural Sciences of the National University of Córdoba. Master in Applied Statistics from the Faculty of Agricultural Sciences, Faculty of Economic Sciences and Faculty of Mathematics, Astronomy and Physics of the National University of Córdoba.

Position: Member of the Academic Administration Council of the Master in Applied Statistics.
University Professor in Agricultural Sciences of the Faculty of Agricultural Sciences of the National University of Córdoba. Professor of the Agricultural Engineering Career. Adjunct Professor (DE) in Statistics and Biometrics, Quantitative Methods for Agricultural Research at the Faculty of Agricultural Sciences of the National University of Córdoba.
Teacher of the Master and Doctorate in Agricultural Sciences. Statistics and Biometrics Course of the Faculty of Agricultural Sciences of the National University of Córdoba.
Coordinating teacher in the Master in Seed Technology of the Faculty of Agricultural Sciences of the National University of Córdoba. Teacher of the Master in Food Science and Technology. Statistics and Design of Experiments Course. FCA - FCQ- FCM-UNC. 2014. Director of the Department of Rural Development of the Faculty of Agricultural Sciences. Resol. HCD-FCA 84/13. UNC. Full member of the Academic Administration Council of the Master in Applied Statistics. Joint master's degree from the Faculty of Agricultural Sciences, Faculty of Economic Sciences and Faculty of Mathematics, Astronomy and Physics. National University of Córdoba Resol. HCD FCA 303/13 - UNC.
Adviser in statistical analysis in the Data Processing Area under the Secretary of General Coordination and Planning of the Faculty of Agricultural Sciences. Resol. HCD-FCA 994/11. UNC. Category III Teacher-Researcher. Year categorization: 2009. Member of the Consulting Service of the Chair of Statistics and Biometry of the Faculty of Agricultural Sciences. UNC. 1990 to date.
Member of the InfoStat statistical software development team.

Marcelo Cabrera, Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Servicio de Cardiología. Córdoba, Argentina.

Surgeon from the National University of Córdoba. Specialist in Cardiology from the Council of Doctors of the Province of Córdoba and the National University of Córdoba. Specialist in Pediatric Cardiology by the Council of Doctors of the Province of Córdoba. Diploma in Basic Biostatistics Applied Mediated with Environment R from the National University of Córdoba.
Training internships: Texas Children Hospital (Houston, USA), Adult Congenital Heart Disease Service; Training stay at Hospital de la Virgen del Rocío (Seville, Spain), Cardiology Service.
Research interests in cardiovascular reconstructive surgery.
Publications: 6 articles published in peer-reviewed scientific journals in the field of cardiovascular surgery

Raquel Dodelson de Kremer, Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas (CEMECO). Córdoba, Argentina. 3 Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Clínica Pediátrica. Córdoba, Argentina.

Surgeon and Doctor of Surgery and Medicine, degrees awarded by the National University of Córdoba. Pediatric specialist. Córdoba Province Council of Doctors.
Honorary Member of the Argentine Genetic Society. Academic Emeritus of the Academy of Medical Sciences of Córdoba. Full Member of the National Academy of Sciences.
Prof. Consultation of the National University of Córdoba. She was the founder and director of the 2018 Center for the Study of Congenital Metabolopathies (CEMECO), Children's Hospital of Córdoba. Pioneer in the study of hereditary metabolic diseases with more than 60 publications in the specialty.

Ernesto Juaneda, Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Servicio de Cardiología. Córdoba, Argentina.

Surgeon from the National University of Córdoba. Pediatric Clinical Residence, Children's Hospital Stma. Trinidad, Córdoba, Argentina. Pediatrician, Ministry of Health of the Province of Córdoba. Children's Cardiologist, Argentine Society of Pediatrics- Argentine Society of Cardiology, Buenos Aires. Pediatric Cardiologist, Medical Council, Province of Córdoba. Doctor of Medicine, Catholic University of Córdoba, Faculty of Medicine, Argentina.
Internships: Pediatric Cardiology Fellowship, Department of Cardiology, Hammersmith Hospital, Royal Postgraduate Medical School, London, England. Pediatric Cardiology Overseas Visitors Fellowship, British Heart Foundation, Department of Pediatric Cardiology, University of London, Hospital for Sick Children, London, England.

Position: Chief Pediatric Cardiology Service, Children's Hospital Stma. Trinidad, Córdoba, Argentina. Pediatric Cardiologist, Pediatrics and Neonatology Service, Sanatorio Allende.
Authorized professor of Pediatric Cardiology and neonatology. Chair of Pediatrics, Faculty of Medicine, Catholic University of Córdoba. 2002 -2010.
Member of the Research, Training, Teaching and Research Committee, Hospital de Niños Stma. Trinidad, Córdoba, Argentina. 1997-2005. Member of the Institutional Committee of Ethics in Health Research (C.I.E.I.S) Hospital Hospital for Children and Adults. 2003-2005.
Research interests Pulmonary hypertension; Non-invasive diagnosis of Congenital Heart Diseases; Quality Quantification and Quality Improvement in Congenital Heart Diseases

Laura E Laróvere, Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas (CEMECO). Córdoba, Argentina. 2 Consejo Nacional de Investigación Científica y Técnica (CONICET), Ministerio de Ciencia, Tecnología e Innovación. Argentina. 3 Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Clínica Pediátrica. Córdoba, Argentina.

Biologist and Doctor in Chemical Sciences, degrees awarded by the National University of Córdoba. Specialist in Human Genetics and Biochemical Genetics. Title granted by the Genetic Society of Argentina
Position: Center for the Study of Inherited Metabolic Diseases (CEMECO), Children's Hospital of Córdoba and Assistant Professor of Pediatrics, Faculty of Medicine, National University of Córdoba, since 1993. Health Researcher of the National Council for Scientific and Technical Research (CONICET)
Research interests in inborn errors of purine and pyrimidine metabolism, urea cycle defects, and pharmacogenetics.
Training Research Program at the Purines Research Laboratory, Guy´s Hospital, London (United Kingdom), Faculty of Biotechnology, University of Gdansk (Poland) and Laboratory of Pediatrics and Neurology, University Medical Center of St. Radboud, Nijmegen (The Netherlands).
Publications: 20 articles published in peer-reviewed scientific journals in the field of inborn errors of metabolism and pharmacogenetics and two book chapters.
Societies / Editorial Committees: Member of the Scientific Committee of the Latin American Society of Birth Errors of Metabolism and Neonatal Screening and Member of the Editorial Committee of the Journal of Birth Errors of Metabolism and Screening (2013-present). Ad hoc evaluator of the Journal Molecular and Genetics Metabolism (2003).

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Pintura del autor Prof. Dr. Roque Alejandro Maffrand.

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Published

2020-12-01

How to Cite

1.
Silvera Ruiz S, Grosso CL, Tablada M, Cabrera M, Dodelson de Kremer R, Juaneda E, Laróvere LE. Efficacy of citrulline supplementation to decrease the risk of pulmonary hypertension after congenital heart disease surgery. A local experience. Rev Fac Cien Med Univ Nac Cordoba [Internet]. 2020 Dec. 1 [cited 2024 Jul. 17];77(4):249-53. Available from: https://revistas.unc.edu.ar/index.php/med/article/view/27936

Issue

Vol. 77 No. 4 (2020)

Section

Original Papers

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