1 . 2018

The research of possible biochemical and morphological markers of “no-reflow” phenomenon in experiment

Abstract

Aim – to research the interrelation between the carbonyl derivatives of proteins and damage of vascular endothelium as potential predictor of the development of «no-reflow» phenomenon in experimental reperfusion injury.

Methods. Experimental study was carried out on Wistar rates according to the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 18.03.1986) and the Order of the Ministry of Healthcare of the Russian Federation «On the ratification of the rules of laboratory practice» N 267 iss. 19.06.2003. The model of reperfusion injury has been performed by cross clamping of the aorta with following conditioning. The activity of lysosomal cysteine proteases, oxidative modification of serum proteins, level of homogenates in the affected vascular wall and intact vascular wall distal to the manipulations were then evaluated. We used transmission electron microscopy the Carl Zeiss Libra 120 (Germany). Statistical evaluation of data was performed according to the relevant methods of mathematical analysis provided by the advanced analytics software package Statistica 10.0. Statistical significance was assessed with the Mann–Whitney U-test.

Results. In experimental reperfusion injury model oxidative stress developed from day 1 to day 7 in serum and by day 3 to day 7 in vascular wall. Oxidative stress in vascular wall has been characterized by the attenuation of adaptive reserve potential and predominance of secondary markers with activity of cathepsins B and L reaching its maximum levels at days 3 and 5, which corresponded to the structural changes in vascular intima.

Conclusion. Increased levels of secondary metabolites of the oxidative stress in vascular wall lead to the damage of endothelial cells, which may determine an important structural element in the pathogenesis of the «no-reflow» phenomenon.

Keywords:«no-reflow» phenomenon, reperfusion, oxidative stress, carbonyl derivatives of proteins, cathepsins, endothelium

Clin. Experiment. Surg. Petrovsky J. 2018; 1 (19): 62–69.

DOI: 10.24411/2308-1198-2018-00009

Received: 16.08.2017. Accepted: 25.01.2018.

References

1. Koval’ M. The phenomenon of "no-reflow" is a fly in the ointment of honey of revascularization. Medical Review [Medical Review]. 2008; 5 (05): 32–6. (in Russian)

2. Van de Werf F., Bax J., Betriu A., et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology. Eur Heart J. 2008; 29: 2909–45.

3. Ito H. No-reflow phenomenon and prognosis in patients with acute myocardial infarction. Nat Clin Pract Cardiovasc Med. 2006; 3: 499–506.

4. Fischell T.A. Pharmaceutical interventions for the management of no-reflow. J Invasive Cardiol. 2008; 20 (7): 374–9.

5. Lee K.W., Norell M.S. Management of «no-reflow» complicating reperfusion therapy. Acute Card Care. 2008; 10 (1): 5–14.

6. Valero S.J., Moreno R., Reyes R.M., et al. Pharmacological approach of no-reflow phenomenon related with percutaneous coronary interventions. Cardiovasc Hematol Agents Med Chem. 2008; 6 (2): 125–9.

7. Lushchak V.I. Free radical oxidation of proteins and its relationship with the functional state of the organism . Biokhimiya [Biochemistry]. 2007; 72 (8): 995–1017. (in Russian)

8. Vasil’ev Y.V., et al. Protein modifications by electrophilic lipoxidation products: adduct formation, chemical strategies and tandem mass spectrometry for their detection and identification. Mass Spectrom Rev. 2013; 33 (3): 157–82.

9. Hristova M., Penev M. Oxidative stress and cardiovascular diseases. Vasc Pharmacol. 2012; 12 (3): 296–303.

10. Abalenikhina Yu.V., Fomina M.A., Isakov S.A. Oxida- tive modification of proteins and changes in the activity of cathepsin L in the spleen of rats under conditions of modeling the deficiency of synthesis of nitric oxide. Rossiyskiy mediko-biologicheskiy vestnik im. akad. I.P. Pavlova [Russian Medical and Biological Bulletin named after acad. I.P. Pavlov]. 2013; (1): 44–8. (in Russian)

11. Dubinina E.E., Burmistrov S.O., Khodov D.A., et al. Oxidative modification of human serum proteins, method of its determination Voprosy meditsinskoy khimii [Questions of Medical Chemistry]. 1995; 41 (1): 24–6. (in Russian)

12. Fomina M.A., Abalenikhina Yu.V. A method for the complex assessment of the content of products of oxidative modification of proteins in tissues and biological fluids. Patent for the invention of the Russian Federation No. 2524667. Bul. 07/27/2014.. (in Russian)

13. Barrett A.J. Cathepsin B, cathepsin H, cathepsin L. Methods Enzymol. 1981; 80: 535–61.

14. Kalinin R.E., Pshennikov A.S., Suchkov I.A. Reperfusion injury of tissues in surgery of lower limb arteries . Novosti khirurgii [Surgery News]. 2015; 23 (3): 348–52. (in Russian)