4.5 Article

Beneficial Effects of RNS60 in Cardiac Ischemic Injury

Journal

CURRENT ISSUES IN MOLECULAR BIOLOGY
Volume 44, Issue 10, Pages 4877-4887

Publisher

MDPI
DOI: 10.3390/cimb44100331

Keywords

RNS60; cardiac ischemic injury; cardiac hypoxia; cardiac energetics; cardioplegia; Custodiol

Funding

  1. Narodowe Centrum Nauki [Preludium 2018/29/N/NZ4/02259, HARMONIA 2016/22/M/NZ4/00678]

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RNS60 has been shown to provide cardioprotection during myocardial hypoxia and cardioplegic arrest, potentially through improved cardiac energetics.
RNS60 is a physically modified saline solution hypothesized to contain oxygen nanobubbles. It has been reported to reduce ischemia/reperfusion injury in a pig model of acute myocardial infarction. We investigated the effects of RNS60 during cardiac hypoxia in mice and as an additive to cardioplegic solution in rat hearts. ApoE(-/-)LDLr(-/-) mice were treated by intravenous injection of RNS60 or saline as a control while monitoring the ECG and post-hypoxic serum release of troponin T and creatine kinase activity. Hearts infused with Custodiol containing 10% RNS60 or saline as the control were subjected to 4 h of 4 degrees C preservation, followed by an assessment of myocardial metabolites, purine release, and mechanical function. RNS60 attenuated changes in the ECG STU area during hypoxia, while the troponin T concentration and creatine kinase activity were significantly higher in the serum of the controls. During reperfusion after 4 h of cold ischemia, the Custodiol/RNS60-treated hearts had about 30% lower LVEDP and better dp/dt(max) and dp/dt(min) together with a decreased release of purine catabolites vs. the controls. The myocardial ATP, total adenine nucleotides, and phosphocreatine concentrations were higher in the RNS60-treated hearts. This study indicates that RNS60 enhances cardioprotection in experimental myocardial hypoxia and under conditions of cardioplegic arrest. Improved cardiac energetics are involved in the protective effect, but complete elucidation of the mechanism requires further study.

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