European Journal of Clinical Pharmacology

, Volume 75, Issue 10, pp 1361–1367 | Cite as

Influence of the aldehyde dehydrogenase 2 polymorphism on the vasodilatory effect of nitroglycerin in infants with congenital heart disease and pulmonary arterial hypertension

  • Tatsuya Nagano
  • Kentaro Ushijima
  • Naoyuki Taga
  • Mamoru Takeuchi
  • Masa-aki Kawada
  • Kenichi Aizawa
  • Yasushi Imai
  • Akio FujimuraEmail author
Clinical Trial



The influence of the aldehyde dehydrogenase 2 (ALDH2) gene polymorphism on the pharmacokinetics and haemodynamics of nitroglycerin (GTN) was determined in human subjects.


Eighteen infants (nine each with and without ALDH2 gene polymorphism) with congenital heart disease and pulmonary arterial hypertension participated in this study. GTN treatment started at a dose of 2 μg/kg/min, and the dose was escalated by 1–2 μg/kg/min until pulmonary vascular resistance (PVR) was reduced by more than 30%. The plasma GTN concentration and PVR were measured at the end of each infusion period.


Plasma GTN concentrations were significantly higher in patients with the ALDH2 gene polymorphism than in those without the polymorphism. Conversely, the reduction in PVR was smaller in patients with the ALDH2 gene polymorphism than in those without.


These data suggest that the ALDH2 gene polymorphism influences the pharmacokinetics and haemodynamics of GTN in human subjects.


ALDH2 polymorphism Congenital heart disease Nitroglycerin Pulmonary hypertension 



This study was supported by a research grant from the Japan Research Foundation for Clinical Pharmacology (K.U.).

We thank the following collaborators for their kind support: Dr. Koichi Kataoka, Dr. Yoji Otsuka, Dr. Hidetaka Iwai and Dr. Kohei Sunoki (Department of Anesthesiology and Critical Care Medicine, Jichi Medical University); Dr. Ko Yoshizumi and Dr. Shinya Ugaki (Division of Paediatric and Congenital Cardiovascular Surgery, Jichi Children’s Medical Center Tochigi, Jichi Medical University); and Ms. Hisae Shiokawa (Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University).

We thank Joe Barber Jr., PhD, from Edanz Group ( for editing a draft of this manuscript.

Author contributions

Conceived of or designed study: Tatsuya Nagano, Kentaro Ushijima, Kenichi Aizawa, Yasushi Imai, Akio Fujimura.

Performed research: Tatsuya Nagano, Naoyuki Taga, Mamoru Takeuchi, Masa-aki Kawada.

Analysed data: Tatsuya Nagano, Kentaro Ushijima.

Contributed new methods or models: Tatsuya Nagano, Kentaro Ushijima.

Wrote the paper: Tatsuya Nagano, Kentaro Ushijima, Yasushi Imai, Akio Fujimura.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest in relation to this work.

Supplementary material

228_2019_2709_MOESM1_ESM.docx (28 kb)
ESM 1 (DOCX 27 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Clinical Pharmacology, Department of PharmacologyJichi Medical UniversityTochigiJapan
  2. 2.Department of Anesthesiology and Critical Care MedicineJichi Medical UniversityTochigiJapan
  3. 3.Faculty of Pharmaceutical SciencesSanyo-Onoda City UniversityYamaguchiJapan
  4. 4.Division of Pediatric and Congenital Cardiovascular Surgery, Jichi Children’s Medical Center TochigiJichi Medical UniversityTochigiJapan

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