A randomized and blinded trial of inhaled nitric oxide in a piglet model of pediatric cardiopulmonary resuscitation

Ryan W. Morgan, Robert M. Sutton, Adam S. Himebauch, Anna L. Roberts, William P. Landis, Yuxi Lin, Jonathan Starr, Abhay Ranganathan, Nile Delso, Constantine D. Mavroudis, Lindsay Volk, Julia Slovis, Alexandra M. Marquez, Vinay M. Nadkarni, Marco Hefti, Robert A. Berg, Todd J. Kilbaugh

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: Inhaled nitric oxide (iNO) during cardiopulmonary resuscitation (CPR) improved systemic hemodynamics and outcomes in a preclinical model of adult in-hospital cardiac arrest (IHCA) and may also have a neuroprotective role following cardiac arrest. The primary objectives of this study were to determine if iNO during CPR would improve cerebral hemodynamics and mitochondrial function in a pediatric model of lipopolysaccharide-induced shock-associated IHCA. Methods: After lipopolysaccharide infusion and ventricular fibrillation induction, 20 1-month-old piglets received hemodynamic-directed CPR and were randomized to blinded treatment with or without iNO (80 ppm) during and after CPR. Defibrillation attempts began at 10 min with a 20-min maximum CPR duration. Cerebral tissue from animals surviving 1-h post-arrest underwent high-resolution respirometry to evaluate the mitochondrial electron transport system and immunohistochemical analyses to assess neuropathology. Results: During CPR, the iNO group had higher mean aortic pressure (41.6 ± 2.0 vs. 36.0 ± 1.4 mmHg; p = 0.005); diastolic BP (32.4 ± 2.4 vs. 27.1 ± 1.7 mmHg; p = 0.03); cerebral perfusion pressure (25.0 ± 2.6 vs. 19.1 ± 1.8 mmHg; p = 0.02); and cerebral blood flow relative to baseline (rCBF: 243.2 ± 54.1 vs. 115.5 ± 37.2%; p = 0.02). Among the 8/10 survivors in each group, the iNO group had higher mitochondrial Complex I oxidative phosphorylation in the cerebral cortex (3.60 [3.56, 3.99] vs. 3.23 [2.44, 3.46] pmol O2/s mg; p = 0.01) and hippocampus (4.79 [4.35, 5.18] vs. 3.17 [2.75, 4.58] pmol O2/s mg; p = 0.02). There were no other differences in mitochondrial respiration or brain injury between groups. Conclusions: Treatment with iNO during CPR resulted in superior systemic hemodynamics, rCBF, and cerebral mitochondrial Complex I respiration in this pediatric cardiac arrest model.

Original languageEnglish (US)
Pages (from-to)274-283
Number of pages10
JournalResuscitation
Volume162
DOIs
StatePublished - May 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

  • Cardiopulmonary resuscitation
  • Cerebral blood flow
  • Hemodynamics
  • In-hospital cardiac arrest
  • Inhaled nitric oxide
  • Laboratory
  • Pediatrics
  • Physiology
  • Pulmonary hypertension
  • Shock

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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