Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Myocardial Interstitial Matrix as Novel Target for Succinic Acid Treatment Strategies during Experimental Hypobaric Hypoxia

Version 1 : Received: 8 November 2018 / Approved: 12 November 2018 / Online: 12 November 2018 (05:16:27 CET)

A peer-reviewed article of this Preprint also exists.

Zadnipryany IV, Sataieva TP, Tretiakova OS, Zukow W. Myocardial interstitial matrix as novel target for succinic acid treatment strategies during experimental hypobaric hypoxia. Russian Open Medical Journal 2019; 8: e0201. Zadnipryany IV, Sataieva TP, Tretiakova OS, Zukow W. Myocardial interstitial matrix as novel target for succinic acid treatment strategies during experimental hypobaric hypoxia. Russian Open Medical Journal 2019; 8: e0201.

Abstract

The myocardial extracellular matrix is not a passive entity, but rather a complex and dynamic microenvironment which represents an important structural and signaling system within the myocardium. Understanding the fundamental role of hypoxia and peroxidation in the genesis of many cardiovascular diseases has stimulated the development of strategies that can enhance the energy-producing functions of cells. Revealing the alterations in cardiac metabolism and function associated with sustained exposure to high altitude advances our understanding of hypoxia-related disease. The study was conducted on 26 adult males of Wistar rats weighing 220–310 g, divided into 3 groups. The first control group consisted of 6 intact animals, the second group included 10 rats which were exposed to hypobaric hypoxia without medication for 30 days. Third group was composed of 10 rats, which were medicated by succinic acid solution which was injected intraperitoneally once a day at the rate of 0.5 mL/100 g of animal body weight 15 minutes before hypoxic exposure for 30 days. Fibrosis in the myocardium inevitably leads to increased myocardial stiffness, resulting in systolic and diastolic dysfunction, neurohormonal activation and, ultimately, heart failure Changes in cardiac highenergy phosphate metabolism may underlie the myocardial dysfunction caused by hypobaric hypoxia. Reduced oxygen delivery by microvascular damage, increased perivascular fibrosis associated with reduced cellular oxygen availability may contribute to contractile failure. Succinic acid combined with inosine acts as a high-energy phosphate reserve, to maintain adenosine triphosphate at levels sufficient to support contractile function.

Keywords

hypobaric hypoxia; myocardium; interstitial space; fibroblasts; fibrosis; succinic acid; rats

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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