CC BY
19
UDC 612.084:615.22
A. A. Volodkin, G. E. Zaikov
MECHANISM OF MYOCARDIAL INFARCTION: PATHOLOGICAL CHANGES IN RATS AFTER
APPLICATION OF ANPHEN SODIUM
Keywords: 1-(carboxy (N-acetylamino) -2- (3', 5'-di-tert-butyl-4'-hydroxyphenyl) -propionate sodium,
epinephrine, myocardial infarction.
Biological properties of a preparation 1-(carboxy (N-acetylamino ) - 2 - (3 ', 5 '-di-tert-butyl-4 '-hydroxyphenyl) -propionate sodium (Anphen-sodium) on epinephrine model of development of a heart attack of a myocardium at rats have been investigated. In an initial stage in experiences "in-vivo" "Anphen-sodium" stops developments of a heart attack of a myocardium with preservation of life of animals.
Ключевые слова: 1-(карбокси)-1-(М-ацетиламино)-2 -(3',5'-ди-трет-бутил-4'- гидроксифенил)-пропионат натрия,
адреналин, инфаркт миокарда.
Исследованы биологические свойства препарата 1-(карбокси)-1-(М-ацетиламино)-2-(3',5'-ди-трет-бутил-4'-гидроксифенил)-пропионата натрия (Анфен-натрий) на адреналиновой модели развития инфаркта миокарда у крыс. В начальной стадии развития инфаркта миокарда в опытах «in-vivo» «Анфен-натрий» приостанавливает развитие инфаркта миокарда с сохранением жизни животных.
Introduction
It is known [1,2], that at disintegration of myocardium cages free radicals that can influence the mechanism of development of a heart attack are formed. Now the myocardial infarction considered as consequence of sharp hydroxaemia because of damage of coronary vessels, and at formation of free radicals reaction with oxygen that can lead to the chain mechanism is possible. This direction in addition strengthens deficiency of oxygen that often leads to a lethal outcome. It is known [3] that in reaction with oxygen are formed peroxyradical the radicals responsible for continuation of chain reaction, and antioxidants inhibited this direction [4]. It is possible to assume that, antioxidant application can render medical effect at a stage of development a myocardial infarction. In the present work as water-soluble and slowly toxic an antioxidant are used 1-(carboxy)-1-(N-acetylamino)- 2 -(3', 5'-di-tert-butyl-4'-hydroxyphenyl)-propionate
sodium (Anphen-sodium) possessing properties of radio- and cancer protectors [5,6]. Diagnostic criterion of a heart attack of a myocardium, along with electrocardiogram methods, tests on "Troponin I" or "Troponin T" [7].
Experimental Part
1 -(Carboxy)-1 -(N-acetylamino)-2-(3', 5' -di-tert-butyl-4' -hydroxyphenyl)-propionate sodium (Anphen-sodium) received on a method [8].
Nuclear magnetic resonance spectrum :H (A2O, 5, m.): 1.36 (s, 18H, 4Bu); 1.96 (s., 3H, COCH3); 3.38 (s, 2H, CH2); 4.70 (s, HOH) ;); 6.42-6.46 (s. ym., 1H, OH); 6.95 (s, 2H, Ar); a nuclear magnetic resonance 13C (A2O, 5, m.): 22.30 (CH3); 29.43 (CH3, 4Bu); 33.64 (CH2); 37.45 (C, 4Bu); 125.94 (CH, Ar); 130.02 (C - CH2, Ar); 139.18 (C-Bu), Ar); 150.80 (C-OH, Ar); 171.14 (C-N (O); 174.30 (C-OO). Let's dissolve in water and a physiological solution.
Studying of biological properties of a preparation "Anphen-sodium" with use of epinephrine model of a heart attack of a myocardium (in updatings
[9, 10]) spent under anaesthetic rats of line Wistar (males, females) weight of 200-220 g. Experimental animals have been divided into two groups on 5 rats in everyone.
First group - epinephrine introduction entered in a dose of 4 mg/kg.
Second group - after epinephrine introduction in (4 mg/kg), to rodents entered a preparation "Anphen-sodium" in a dose of 50 mg/kg.
For an estimation of efficiency of application of a preparation supervised following indicators:
• Survival rate of animals after epinephrine introduction - changes on the electrocardiogram which has been removed at 4 hours after introduction by an animal of epinephrine. Cardiogrames removed on electrocardiograph CardiMax FX-7102 in II standard assignment (II - left back and right an extremity lobby) in back position; -Presence in blood of rats Troponin (TnI) in 4 hours after epinephrine introduction. Maintenance definition Troponin I carried out test device Troponin I-Heck-1, testing on formation of the painted strip at interaction of antibodies to "TnI" from the sample of blood.
Results
In case application of "Anphen-sodium" after epinephrine introduction prevented survival of experimental animals were in 4 of 5 experiments of testing rates. Before tests animals behaved usually, deviations in their behaviour, forage and water consumption has not been noted. Electrocardiograms of all animals were in norm (Figure 1).
In first group, death rate within the first 48 hours after adrenaline introduction were100 %. Observed at opening of the fallen animals pathoanatomical changes specified in a hypostasis of lungs, apparently, cardio-nature.
Rats of second group at 24 hours after introduction of epinephrine and "Anphen-sodium" remained live though in the first 2 days showed strong block; at two rats of this group it was marked breath by
a mouth, spasms; at 4 hours after introduction of epinephrine of the electrocardiogram have shown.
I
I
Fig. 1 - Electrocardiograme of a rat in the second standard assignment before tests
First Group: The registration of lifting of segment "ST" against sharp reduction of height of tooth "R" and delays of a warm rhythm. The height of tooth "R" decreases at the expense of formation of a zone of damage to a myocardium (Figure 2).
'Vaaa/^aaa/V^
Fig. 2 - Electrocardiograme of a rat in the second standard assignment from the first group
At 48 hours after introduction of epinephrine of two rats were decapitate. In blood has been found out "Troponin I" Second Group: Electrocardiograme registers lifting of segment «ST» above an isoline and its merge to positive tooth "T" (Figure 3). For 20 days of 4 rats from 5 experimental continued to live with signs of languid behaviour.
IJ r
1
Fig. 3 - Electrocardiograme of a rat in the second standard assignment from the second group
Discussion
Influence of antioxidants on processes in a myocardium in conditions hypoxaemia was marked earlier [11], however their role in heart attack
development was not discussed. Taking into account radical processes at necrosis of ischaemia cardiomiotsity it is necessary to consider process of interaction of oxygen with radicals that predetermines possibility of development of a heart attack of a myocardium on the chain mechanism.
Participation in this process of an antioxidant slows down speed of chain reaction that should lead to more limited area of a heart attack of a myocardium with preservation of viability of an organism. Structure "Anphen-sodium" provides high anti oxidising parametres and ability to take root in lipid a cover erythrocytus that gives to the given preparation unique properties.
Results confirm that in an initial stage of development of a heart attack of a myocardium in experiences in-vivo on rats "Anphen-sodium" renders medical result. On the electrocardiogramme of an animal after introduction of epinephrine and further it is consecutive fysiological a solution "Anphen-sodium" lifting of segment "ST" (Figure 3) is observed that can specify in an initial stage of development of a myocardium infarction. At the same time the height of tooth "R" does not change, whereas in experiment from fist group (Figure 2) tooth "R" is hardly noticeable. In comparison with control the survival rate makes 4 animals from 5 experimental whereas in control 100 % death rate are marked. This result can be interpreted as consequence of inhibition of development of a heart attack of a myocardium under the influence of an antioxidant and partially radical nature of this pathological process. At a stage before infarct conditions as a result hypoxaemia there is an accumulation of radicals to some critical concentration and further the chain mechanism is started interactions of radicals with oxygen (a stage of development of a heart attack of a myocardium). The mechanism of similar processes is described [4] which proceeds under the scheme 1:
RH
R
R + 02-
R02
R02 + RH
ro2h
R
R02 + InH
R02H + In
(1) (2)
(3)
(4)
Formation of radicals from cardiomiotsity (R) at a myocardial infarction is known [2,3] (reaction typel). Reactions type (2) and (3) specify in the oxygen expense on the chain mechanism that can correspond to a stage of development of a heart attack on the chain mechanism. Antioxidants (InH) on reaction (4) stop this process.
Conclusion
Qualitative results on the basis of electrocardiograms of experimental animals confirm efficiency of a preparation "Anphen-sodium" in possibility of prevention of development of a heart attack with a lethal outcome.
References
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© A. A. Volodkin - Doctor of Chemical Sciences, Professor, Leading Researcher, N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia; G. E. Zaikov - Doctor of Chemical Sciences, Professor of Plastics Technology Department, Kazan National Research Technological University, Russia, [email protected].
© А. А. Володькин - доктор химических наук, профессор, ведущий научный сотрудник, Институт биохимической физики им. Н.М. Эмануэля РАН, Москва, Россия; Г. Е. Заиков - доктор химических наук, профессор кафедры Технологии пластических масс, Казанский национальный исследовательский технологический университет, Россия, [email protected].
