Myocardial interstitial matrix as novel target for succinic acid treatment strategies during experimental hypobaric hypoxia

• Main Authors: Igor V. Zadnipryany, Tatiana P. Sataieva, Olga S. Tretiakova, Walery Zukow
• Format: Article
• Language: English
• Published: Limited liability company «Science and Innovations» (Saratov) 2019-06-01
• Series: Russian Open Medical Journal
• Subjects: rats; myocardium; hypobaric hypoxia; interstitial space; fibroblasts; fibrosis; succinic acid
• Online Access: http://www.romj.org/node/274

Objective — Quantitative morphological studies of myocardial cellular elements. Aim of research is to study myocardial interstitial matrix with and without succinic acid treatment in the rats exposed to intermittent hypobaric hypoxia. Material and Methods — 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. Results — In the second group almost the entire stroma was consisting of the thickened collagen fibers and proliferating cells of the connective tissue. Their total number increased relatively to the control by 31% initiating the processes of collagenases. An increase in the number of myofibroblasts which was observed in the hypoxic rat heart in the second group followed by high MPP-9 expression. Hypoxic effects in the third group were not significantly different from control according to the observed changes in the stroma. In rats of the third group the capillary diameter exceeded the indicator of the second group, but was significantly lower than the control indicator. Accordingly, compared with the series without correction, the cross-sectional area of the capillaries was increased – 28.44±0.14 μm2 against 24.53±0.20 μm2. The total cross-sectional area of the capillaries is 0.77±0.10 x103 μm2. The relative surface area of the vascular area was lower than the control by 21.8%. Conclusion ― Fibrosis in the myocardium inevitably leads to increased myocardial stiffness, resulting in systolic and diastolic dysfunction, neurohormonal activation and, ultimately, heart failure caused by hypobaric hypoxia. Reduced oxygen delivery by microvascular damage, increased perivascular fibrosis 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.