Manipulation of Nitric Oxide Levels via a Modified Hydroxyethyl Starch Molecule

Ugur Aksu*, Can Ince, Silke Baasner, Johannes Hermle, Corinna Lupp, Dominik Heckmann, Frank Nocken, Martin Westphal

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Introduction: Although the improving effect of nitric oxide (NO) donors has experimentally been demonstrated in shock, there are still no NO donor medications clinically available. Thiol-nitrosothiol-hydroxyethyl starch (S-NO-HES) is a novel molecule consisting of NO coupled to a thiolated derivative of hydroxyethyl starch (HES). It was aimed to assess the ability of S-NO-HES to serve as an NO donor under a variety of in vitro simulated physiologic conditions, which might be the first step to qualify this molecule as a novel type of NO donor-fluid.

Methods: We studied the effect of temperature on NO-releasing properties of S-NO-HES in blood, at 34°C, 37°C, and 41°C. Ascorbic acid (Asc) and amylase were also tested in a medium environment. In addition, we evaluated the activity of S-NO-HES in the isolated aortic ring and Langendorff-perfused heart setup.

Results: The NO release property of S-NO-HES was found at any temperature. Asc led to a significant increase in the production of NO compared to S-NO-HES incubation (P < 0.05). The addition of amylase together with Asc to the medium further increased the release of NO (P < 0.05). S-NO-HES exerted significant vasodilatory effects on phenylephrine precontracted aortic rings that were dose-dependent (P < 0.01). Furthermore, S-NO-HES significantly increased the heart rate and additionally reduced the duration of the cardiac action potential, as indicated by a reduction of QTc-B values (P < 0.01).

Conclusions: We demonstrated for the first time that the S-NO-HES molecule exhibited its NO-releasing effects. The effectiveness of this new NO donor to substitute NO deficiency under septic conditions or in other indications needs to be studied.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalJournal of Surgical Research
Early online date9 Sept 2022
Publication statusPublished - Jan 2023

Bibliographical note

Funding Information: This study was carried partly funded by a grant from Fresenius Kabi.

Publisher Copyright: © 2022 Elsevier Inc.


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