Manipulation of Nitric Oxide Levels via a Modified Hydroxyethyl Starch Molecule


AKSU U., Ince C., Baasner S., Hermle J., Lupp C., Heckmann D., ...More

Journal of Surgical Research, vol.281, pp.1-12, 2023 (Peer-Reviewed Journal) identifier identifier

  • Publication Type: Article / Article
  • Volume: 281
  • Publication Date: 2023
  • Doi Number: 10.1016/j.jss.2022.08.005
  • Journal Name: Journal of Surgical Research
  • Journal Indexes: Science Citation Index Expanded, Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.1-12
  • Keywords: Hydroxyethyl starch, Langendorff-perfused heart, Nitric oxide donor, Vasodilation

Abstract

© 2022 Elsevier Inc.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.