Veno-Arterial Extracorporeal Membrane Oxygenation (ECMO) Impairs Bradykinin-Induced Relaxation in Neonatal Porcine Coronary Arteries

Livia Provitera, Giacomo S Amelio, Matteo Tripodi, Genny Raffaeli*, Francesco Macchini, Ilaria Amodeo, Silvia Gulden, Valeria Cortesi, Francesca Manzoni, Gaia Cervellini, Andrea Tomaselli, Gabriele Zuanetti, Caterina Lonati, Michele Battistin, Shady Kamel, Valeria Parente, Valentina Pravatà, Stefania Villa, Eduardo Villamor, Fabio MoscaGiacomo Cavallaro

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Extracorporeal membrane oxygenation (ECMO) is a lifesaving support for respiratory and cardiovascular failure. However, ECMO induces a systemic inflammatory response syndrome that can lead to various complications, including endothelial dysfunction in the cerebral circulation. We aimed to investigate whether ECMO-associated endothelial dysfunction also affected coronary circulation. Ten-day-old piglets were randomized to undergo either 8 h of veno-arterial ECMO (n = 5) or no treatment (Control, n = 5). Hearts were harvested and coronary arteries were dissected and mounted as 3 mm rings in organ baths for isometric force measurement. Following precontraction with the thromboxane prostanoid (TP) receptor agonist U46619, concentration-response curves to the endothelium-dependent vasodilator bradykinin (BK) and the nitric oxide (NO) donor (endothelium-independent vasodilator) sodium nitroprusside (SNP) were performed. Relaxation to BK was studied in the absence or presence of the NO synthase inhibitor Nω-nitro-L-arginine methyl ester HCl (L-NAME). U46619-induced contraction and SNP-induced relaxation were similar in control and ECMO coronary arteries. However, BK-induced relaxation was significantly impaired in the ECMO group (30.4 ± 2.2% vs. 59.2 ± 2.1%; p < 0.0001). When L-NAME was present, no differences in BK-mediated relaxation were observed between the control and ECMO groups. Taken together, our data suggest that ECMO exposure impairs endothelium-derived NO-mediated coronary relaxation. However, there is a NO-independent component in BK-induced relaxation that remains unaffected by ECMO. In addition, the smooth muscle cell response to exogenous NO is not altered by ECMO exposure.

Original languageEnglish
Article number2083
Number of pages14
JournalBiomedicines
Volume10
Issue number9
DOIs
Publication statusPublished - 25 Aug 2022

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