Author + information
- Received September 26, 2018
- Revision received November 6, 2018
- Accepted November 6, 2018
- Published online April 29, 2019.
- Alexis R. Cole, BSa,
- Dorothy A. Perry, MBChBa,b,
- Ali Raza, MDa,b,
- Arthur P. Nedder, DVMc,
- Elizabeth Pollack, DVM Candidatec,
- William L. Regan, CCP, LPd,
- Sarah J. van den Bosch, MSa,
- Brian D. Polizzotti, PhDa,b,
- Edward Yang, MDe,f,
- Daniel Davila, MDg,h,
- Onur Afacan, MDe,f,
- Simon K. Warfield, PhDe,f,
- Yangming Ou, PhDb,e,f,
- Brenda Sefton, PAd,
- Allen D. Everett, MDi,
- Jeffrey J. Neil, MD, PhDe,f,
- Hart G.W. Lidov, MD, PhDh,j,k,
- John E. Mayer, MDd,l and
- John N. Kheir, MDa,b,∗ ()
- aDepartment of Cardiology, Boston Children’s Hospital, Boston, Massachusetts
- bDepartment of Pediatrics, Harvard Medical School, Boston, Massachusetts
- cAnimal Resources at Children’s Hospital, Boston Children’s Hospital, Boston, Massachusetts
- dDepartment of Cardiovascular Surgery, Boston Children’s Hospital, Boston, Massachusetts
- eDepartment of Radiology, Boston Children’s Hospital, Boston, Massachusetts
- fDepartment of Radiology, Harvard Medical School, Boston, Massachusetts
- gDepartment of Neurology, Boston Children’s Hospital, Boston, Massachusetts
- hDepartment of Neurology, Harvard Medical School, Boston, Massachusetts
- iDivision of Pediatric Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
- jDepartment of Pathology, Boston Children’s Hospital, Boston, Massachusetts
- kDepartment of Pathology, Harvard Medical School, Boston, Massachusetts
- lDepartment of Surgery, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. John Kheir, Department of Cardiology, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115.
• Inhaled hydrogen gas has been shown to temper the sequelae of ischemic insults. Its application in cardiopulmonary bypass has not been investigated.
• Neonatal swine were cannulated to cardiopulmonary bypass and exposed to prolonged circulatory arrest (75 min at 25°C). Swine were randomized to treatment with or without inhaled 2.4% hydrogen gas mixtures for 24 h during and following ischemic injury. Hydrogen-treated swine exhibited significantly less severe brain injury than controls, as quantified by clinical examination, serology, magnetic resonance-graded volume of injury, and histopathology. Hydrogen treatment also decreased renal injury.
• The administration of inhaled 2.4% hydrogen gas mixtures through a standard ventilator and anesthesia machine were safe, even in the setting of electrocautery.
This study used a swine model of mildly hypothermic prolonged circulatory arrest and found that the addition of 2.4% inhaled hydrogen gas to inspiratory gases during and after the ischemic insult significantly decreased neurologic and renal injury compared with controls. With proper precautions, inhalational hydrogen may be administered safely through conventional ventilators and may represent a complementary therapy that can be easily incorporated into current workflows. In the future, inhaled hydrogen may diminish the sequelae of ischemia that occurs in congenital heart surgery, cardiac arrest, extracorporeal life-support events, acute myocardial infarction, stroke, and organ transplantation.
Dr. Kheir is supported by American Heart Association grant 15GRNT25700161; and by philanthropic donations from the Hess Family Cardiac Innovation Fund, the Furber Family Innovative Therapies Fund, and Lindsay Bartels (a donor who provided some financial support for the study). Dr. Everett is a consultant for Immunarray LLC; and holds patents through Johns Hopkins University assigned to Immunarray, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and U.S. Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received September 26, 2018.
- Revision received November 6, 2018.
- Accepted November 6, 2018.
- 2019 The Authors