Резюме
Залюбовська О.І., Березнякова М.Є., Литвинова О.М., Зленко В.В., Фоміна Г.П., Карабут Л.В., Березняков А.В. Вивчення впливу хінолінперадоріна на коагуляаційну активність системи лімфи при інфаркті міокарда.
Встановлено, що в умовах гострого інфаркту міокарда знижується рівень лімфодренажу і наростають процеси коагуляції. Хінолінперадорін нормалізує показники коагуляції та сприяє сприятливому перебігу захворювання. Зміна циркуляції лімфи тісно корелює з тяжкістю захворювання.
Ключові слова: коагуляційна активність, лімфатична система, інфаркт міокарда, хінолінперадорін.
Резюме
Залюбовская О.И., Березнякова М.Е., Литвинова О.М., Зленко В.В., Фомина Г.П., Карабут Л.В., Березняков А.В. Изучение влияния хинолинперадорина на коагуляационную активность системы лимфы при инфаркте миокарда.
Установлено, что в условиях острого инфаркта миокарда снижается уровень лимфодренажа и нарастают процессы коагуляции. Хинолинперадорин нормализует показатели коагуляции и способствует благоприятному течению заболевания. Изменение циркуляции лимфы тесно коррелирует с тяжестью заболевания.
Ключевые слова: коагуляционная активность, лимфатическая система, инфаркт миокарда, хинолинперадорин.
Summary
Zaliubovska O.I., Bereznyakova M.E., Litvinova O.N., Zlenko V.V., Fomina G.P., Karabut L.V., Bereznyakov A.V. Study of influence hinolinperadorin on the coagulation activity system lymph  in myocardial infarction.
The coagulation of lymph was found to be sharply increased and the rate of lymph drainage slowed dawn in acute myocardial infarction. Hinolinperadorin normalized these indices and was thus conducive to a favourable course of the disease. The changes of lymph circulation closely correlated with the severity of the disease.
Key words: coagulation activity, system lymph, myocardial infarction, hinolinperadorin.

УДК 616.12-008.318-06:612.013.7

Національний фармацевтичний університет (Харків)

Национальный фармацевтический университет (Харьков)

61002, г. Харьков, ул. Пушкинская, 53

National University of Pharmacy (Kharkov)

Ukraine, 61002, Kharkov, 53, str. Pushkinska

postavnaya@list.ru

Introduction. Violation of lymph outflow from cardiac muscle damage area leads to development of interstitial edema, aggravates microcirculation disturbance in coronary vessel obliteration area [1, 2].

The object of work is to study the effect of chinoline peradorine (chinoline derivative of carboxylic acids) on lymph circulation wrapping activity and lymph drainage function of cardiac muscle under acute cardiac infarction.  

Work connection with research programs, plans, projects. This research was performed under research plan of National University of Pharmacy, project “Pharmacological Studies of Bioactive Substances and Drugs of Synthetic and Biological Origin, Their Application in Medical Practice”. 

Research material and methods

Experiments were performed on 45 Chinchilla rabbits with weight of 2,2 - 3,2 kg. In 5 rabbits the lymph coagulation condition and lymph outflow rate (lymphorragic syndrome) was studied in intact condition.

In the rest of animals acute cardiac infarction was imitated by tying upper third of anterior interventricular artery. The dynamics of acute cardiac infarction progress was monitored by ECG registration and determination of creatine phosphokinase (CPK) in blood serum by spectrophotometry using Chemaiol standard reagent set. The blood was taken from auricular limbic vein. ECG was registered in intact condition and within 30 days, CPK at the beginning of experiment as well as within 7 days after imitation of infarction. Group 1 (20 rabbits) served as control, 20 animals of Group2 within 1,5 hours  after imitation of infarction were intravenously administered a single effective 40 mg/kg dose of chinoline peradorine substance. Lymph was taken by drainage of thoracic lymphatic duct mouth [3].  Lymph outflow rate was expressed in mL per minute per 1kg of body mass. Lymph coagulation activity was estimated in dynamics on the 1^st, 3^rd, 7^th, 15^th and 30^th day using common methods: determination of coagulation time, recalcification time, heparin tolerance, heparin time, prothrombin index, thrombin time, fibrinogen concentration [4,5]. Surgeries were made under Nembutal narcosis (40 mg /kg), at the end of experiment animals were deadened by air embolism.

Results and discussion

As seen from the data in Tables 1 and 2, in 1 day after tying of coronary artery lymph coagulation rate substantially increased, coagulation time and recalcification time reduced, heparin tolerance increased more than 2.5 times, prothrombin index and fibrinogen concentration increased by 56 and 183% respectively. At the same period lymph outflow rate was reduced to 0,034 ± 0,006 mL/min (initially 0,068 ± 0,007 mL/min). ECG showed signs of acute cardiac infarction (formation of QSIV 2-3 complex and sharply raised ST segment), confirmed by actual increase of CPK activity (83,4 ± 9, 2 U/L Р <0,001).

Table 1

Alteration of lymph coagulation indices under acute cardiac infarction

(М ± m)

Note: Figures in parenthesis refer to alteration of indices in % rate of initial values taken as 100. Initial values of prothrombin index and fibrinogen concentration are taken as 1.

Asterisks denote adequacy of difference with respective initial data:
one asterisk - Р <0,001, two asterisks - Р <0,01, three asterisks - Р <0,05

Table 2

Alteration of lymph coagulation indices under acute cardiac infarction with administration of chinoline peradorine substance

(М ± m)

Note: Validity was calculated in relation to respective values of control group at the same periods of observation. Rest of symbols is identical to those in Table 1.

In animals of Group 2 after administration of chinoline peradorine substance the course of infarction was more favorable. Alterations of lymph coagulation were marked by reduction of heparin tolerance by 69%, more than 1,6 times decrease  of prothrombin index as compared with control group, substantial increase of heparins and thrombin time (221 and 233% respectively), fibrinogen concentration was reduced 2,5 times. Lymph outflow velocity increased more than 4 times as compared with controls (0,141 ± 0,015 mL / min) which was indicative of intensified lymph drainage, thus, better removal of cardiac metabolism toxic products [8,9].  Sharply decreased CPK activity (34,8 ± 9,1 U/L Р <0,001) in blood serum and improved electrocardiography data  (QS complex was not formed, reduced tooth voltage in thoracic abduction and obliquely raised ST segment in almost all abductions) also confirmed positive effect [6,7].

On the 3^rd day the animals of Group 1, who had a necrosis nidus found in basin of ligated coronary artery, judging from data determined by ECG and CPK, showed signs of hypercoagulation remained in lymph, lymph outflow was 69% of initial level. But in animals who obtained chinoline peradorine substance, in that period a clear trend to normalization of lymph coagulation was seen. Lymph outflow velocity was 0,152 ± 0,007 mL / min per 1 kg of body mass, 3 times better than in controls. ECG was improving, CPK activity in blood serum was weakening [10,11].

Beginning from the 7^th day of study the lymph coagulant activity of control animals was approaching initial values, anti-coagulation system was activated which was confirmed by definite increase of heparin time. Lymph outflow velocity remained within the range of initial values, ECG pattern and CPK activity showed normalization trend. Even more expressed shifts in this direction were observed in animals that were administered chinoline peradorine substance.

It must be noted that within the following periods of study heparin and thrombin time values were higher than initial ones, whereas prothrombin index and fibrinogen concentration remained reduced up to the end of observation. Consequently, we may state that chinoline peradorine administration has an expressed hypocoagulation effect and stimulated lymph anti-coagulation actvity. Conclusion

Chinoline peradorine showed an expressed hypocoagulation effect in experiment as well as assisted in acceleration of cardiac lymph draining function.

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