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A Novel Pharmacological Strategy with Carbon Monoxide in Kidney and Heart Transplantation

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Gasotransmitters in Organ Transplantation

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Abstract

Carbon monoxide (CO) was historically regarded solely as a poisonous gas that binds to hemoglobin and reduces oxygen-carrying capacity of blood at high concentrations. However, recent findings show that it is endogenously produced in mammalian cells as a by-product of heme degradation by heme oxygenase, and has received a significant attention as a medical gas that influences a myriad of physiological and pathological processes. At low physiological concentrations, CO exhibits several therapeutic properties including antioxidant, anti-inflammatory, anti-apoptotic, anti-fibrotic, anti-thrombotic, anti-proliferative and vasodilatory properties, making it a candidate molecule that could protect organs in various pathological conditions including cold ischemia-reperfusion injury (IRI) in kidney and heart transplantation. Cold IRI is a well-recognized and complicated cascade of interconnected pathological pathways that poses a significant barrier to successful outcomes after kidney and heart transplantation. A substantial body of preclinical evidence demonstrates that CO gas and CO-releasing molecules (CO-RMs) prevent cold IRI in renal and cardiac grafts through several molecular and cellular mechanisms. This chapter discusses recent advances in research involving the use of CO as a novel pharmacological strategy to attenuate cold IRI in preclinical models of kidney and heart transplantation through its administration to the organ donor prior to organ procurement or delivery into organ preservation solution during cold storage and to the organ recipient during reperfusion and after transplantation. The chapter also discusses the underlying molecular mechanisms of cyto- and organ protection by CO during transplantation, and suggest its clinical use in the near future to improve long-term transplantation outcomes.

This chapter is a modified version by the same author in the publication titled Application of carbon monoxide in kidney and heart transplantation: A novel pharmacological strategy for a broader use of suboptimal renal and cardiac grafts. Pharmacol Res. 2021; 173:105883.

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  1. Department of Surgery, Division of Urology, London Health Sciences Center, University of Western Ontario, London, ON, Canada

    George J. Dugbartey

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Dugbartey, G.J. (2024). A Novel Pharmacological Strategy with Carbon Monoxide in Kidney and Heart Transplantation. In: Gasotransmitters in Organ Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-031-48067-6_7

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