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. 2022 Mar;163(3):841-849.e1.
doi: 10.1016/j.jtcvs.2020.11.150. Epub 2020 Dec 10.

Safety of continuous 12-hour delivery of antimicrobial doses of inhaled nitric oxide during ex vivo lung perfusion

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Free article

Safety of continuous 12-hour delivery of antimicrobial doses of inhaled nitric oxide during ex vivo lung perfusion

Vinicius S Michaelsen et al. J Thorac Cardiovasc Surg. 2022 Mar.
Free article

Abstract

Introduction: High-dose nitric oxide (NO) has been shown effective against a variety of micro-organisms in vitro, including common bacteria found in donor organs. However, clinical obstacles related to its implementation in vivo are the formation of methemoglobin and the accumulation of toxic nitrogen compounds. Ex vivo lung perfusion (EVLP) is a platform that allows for organ maintenance with an acellular perfusion solution, thus overcoming these limitations. The present study explores the safety of continuous high-dose inhaled (iNO) during EVLP for an extended period of 12 hours.

Methods: Lungs procured from Yorkshire pigs were randomized into control (standard ventilation) and treatment (standard ventilation + 200 ppm iNO) groups, then perfused with an acellular solution for 12 hours (n = 4/group). Lung physiology and biological markers were evaluated.

Results: After 12 hours of either standard EVLP or EVLP + 200 ppm iNO, we did not notice any significant physiologic difference between the groups: pulmonary oxygenation (P = .586), peak airway pressures (P = .998), and dynamic (P = .997) and static (P = .908) lung compliances. In addition, no significant differences were seen among proinflammatory cytokines measured in perfusate and lung tissue. Importantly, most common toxic compounds were kept at safe levels throughout the treatment course.

Conclusions: High-dose inhaled NO delivered continuously over 12 hours appears to be safe without inducing any significant pulmonary inflammation or deterioration in lung function. These findings support further efficacy studies to explore the use of iNO for the treatment of infections in donor lungs during EVLP.

Keywords: ex vivo lung perfusion; inhaled gas therapies; lung transplantation; nitric oxide.

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Comment in

  • Commentary: Say yes to NO!
    Benazzo A, Hoetzenecker K. Benazzo A, et al. J Thorac Cardiovasc Surg. 2022 Mar;163(3):850-851. doi: 10.1016/j.jtcvs.2020.12.061. Epub 2021 Jan 12. J Thorac Cardiovasc Surg. 2022. PMID: 33451842 No abstract available.
  • Commentary: To use or not to use…Is NO the answer?
    McCurry KR, Okamoto T, Ayyat KS. McCurry KR, et al. J Thorac Cardiovasc Surg. 2022 Mar;163(3):851-852. doi: 10.1016/j.jtcvs.2020.12.074. Epub 2020 Dec 25. J Thorac Cardiovasc Surg. 2022. PMID: 33518386 No abstract available.

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