RU2364947C1 - Method of simulation of chronic toxic arterial hypertension and cardiopathy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns experimental medicine, namely experimental cardiology and can be used for simulation of chronic toxic arterial hypertension and cardiopathy. It is ensured by daily introduction into a stomach of experimental animals of lead acetate solution once a day in a dose 40 mg/kg metal basis. Unit of solution 0.2 ml fits lead 8 mg.

EFFECT: ensured adequate simulation.

1 ex, 3 tbl, 1 dwg

Description

The invention relates to medicine, experimental biology, ecology, toxicology and can be used to study the mechanisms of toxic effects of heavy metals, in particular lead, on the function of the cardiovascular system.

Environmental lead pollution is one of the most important environmental problems (Akhmetzyanova E.X. et al. 2006), because lead according to the World Health Organization belongs to the group of toxic metals of hazard class I (Kirsankina E.V. 2003). Penetrating into the human body, lead affects almost all organs and systems of the body. Being a natural system of transport of substances in the body, the cardiovascular system is one of the first to undergo the toxic effects of heavy metal. Lead and its compounds contribute to the formation of cardiovascular disease, being a risk factor in the development of neurocirculatory dystonia, myocardial dystrophy, arterial hypertension (Artamonova V.G. et al. 1998). In workers, when lead is exceeded in the air of the working zone, changes in the functional state of the heart, intracardiac and peripheral hemodynamics are determined (Gatagonova T.M. 1995). Changes in the cardiovascular system in such individuals are usually manifested by hypertension and increased vascular tone (Gatagonova T.M. 1999).

Closest to the claimed is a method for modeling malignant arterial hypertension using prostaglandin F2a, taken as a prototype (Pat. 2004107862 Russian Federation. IPC G09B 23/28. Method for modeling malignant arterial hypertension / Rukhinin A.Yu., Savchuk V.I., Sokolova RI; Russian State Medical University. - No. 2004107862/14; application. March 17, 2004; publ. September 10, 2005 // Bull. - 25), which consists in the fact that animals carry out infusion-droplet administration of prostaglandin F2a into the femoral vein 3 times with an interval of 2 days a dose of 1.25-1.5 mg in 5 ml of 5% glucose solution for 40-60 min.

The disadvantage of this method is that it does not study the long-term effects of a toxic drug on the body, and as a substance that causes an increase in blood pressure, a drug is used that is not present in the environment and is not a pollutant. The injected drug prostaglandin F2a has the following pronounced side effects: cardiac arrest, congestive heart failure, atrioventricular heart block of the II degree, ventricular arrhythmia, bradycardia (VIDAL Medication Guide, 1998), which severely limits the use of this drug as a substance that increases blood pressure.

The invention is aimed at solving the problem of developing a method for modeling chronic toxic arterial hypertension and cardiopathy.

The solution to this problem allows us to more fully study the pathophysiological mechanisms of the development of arterial hypertension and cardiopathy during chronic exposure to lead, to create a method for modeling chronic toxic arterial hypertension and cardiopathy, which increases reproducibility, is convenient for conducting an experiment on animals, and is economically viable.

To achieve this technical result, the claimed invention is a method for modeling chronic toxic arterial hypertension and cardiopathy, comprising administering a toxic substance to experimental animals, characterized in that a lead acetate solution is introduced into the stomach 1 time per day daily at a dose of 40 mg / as toxic substance. kg in terms of metal, where 8 mg of lead per unit of solution equal to 0.2 ml.

This method differs from the prototype in the use of a toxic substance - lead acetate, which is widespread in the environment, which is introduced through a tube into the stomach.

Between the distinguishing features of the claimed invention and the technical result there is the following causal relationship: prolonged administration of lead acetate at a dose of 40 mg / kg leads to the development of chronic toxic arterial hypertension and cardiopathy, which is a convenient and close to natural conditions model.

According to the information available to the authors, the set of essential features characterizing the essence of the claimed invention is not known, which allows us to conclude that the invention meets the criterion of "novelty."

According to the authors, the essence of the claimed invention should not be obvious to specialists from a known level of medicine, since it does not reveal the above possibility of obtaining a method for modeling chronic toxic arterial hypertension and cardiopathy, which allows us to conclude that the criterion is “inventive step”.

The set of essential features characterizing the essence of the invention, in principle, can be repeatedly used in medicine to obtain a result consisting in a more accurate and easily reproducible method for the development of chronic toxic arterial hypertension and cardiopathy, which allows us to conclude that the invention meets the criterion of "industrial applicability."

This method is as follows.

To obtain a toxic substance, lead acetate is dissolved in sterile distilled water in such a way that 8 mg of lead (in terms of metal) falls per unit solution of 0.2 ml. For every 100 g of rat weight, 0.1 ml of a toxic solution is injected, which is not an excessive water load on the body of the experimental animal. A solution of lead acetate is injected through an atraumatic tube into the stomach at a dosage of 40 mg / kg, daily 1 time per day for 14 days in one group of animals. At the end of the experiment, the rats were killed using thiopental. For histological studies, tissue samples (heart) were fixed in 10% neutral formalin, and then subjected to paraffin embedding followed by preparation of sections 7-8 microns thick. Sections were stained with hematoxylin and eosin. The sections were studied in transmitted light using a Mikmed-1 microscope under a magnification of 80 × 200 × 400.

The essence of the method is confirmed morphologically. The drawing illustrates the morphological signs of cardiopathy. Histological examination of the heart in experimental animals in group No. 1 revealed dystrophic changes in muscle fibers (a), uneven staining with eosin (b), fragmentation and breakdown of fibers (c). The stroma is edematous, the vessels are full-blooded, their wall with signs of plasma impregnation and perivascular edema.

Example. Rats of Wistar male weighing 200-300 grams were injected with a solution of lead acetate at a dose of 40 mg / kg every day for 14 days through a tube into the stomach. At the end of the experiment (14 days) under the conditions of intraperitoneal anesthesia with sodium thiopental, the mean arterial pressure (SBP) was measured invasively (blood method) in all groups of animals through a plastic catheter filled with a 10% solution of heparin injected into the right femoral artery with an electroanometer. Registration was carried out on an MX-04 monitor with printout of data on an Epson LX-1050 + printer. According to special formulas, the cardiac index (SI) and specific peripheral vascular resistance (OSS) were calculated.

The results of the study showed that in rats with intragastric administration of lead acetate there was a significant increase (p <0.001) in mean arterial pressure (SBP) compared with the intact group (Table 1). Arterial hypertension in the experimental group of animals is associated with a significant increase (p <0.001) in specific peripheral vascular resistance (Table 3). At the same time, a decrease in the cardiac index (p <0.02) was determined in the experimental group of animals (Table 2), which was due to the presence of dystrophic changes in the myocardium, which developed as a result of prolonged toxic effects of lead on myocardial structural formations, which was confirmed by histological research (drawing).

Table 1. The mean arterial pressure against the background of intragastric administration of lead acetate at a dose of 40 mg / kg (M ± m). Experience Conditions Stat. indicator Mean arterial pressure (mmHg) Background M ± m 101.7 ± 1.43 14 days lead acetate (40 mg / kg) M ± m 120.2 ± 2.06 p *) Note: (*) - significant (p <0.001) change compared to the background.

Table 2. Change in the value of the cardiac index against the background of intragastric administration of lead acetate at a dose of 40 mg / kg (M ± m). Experience Conditions Stat. indicator Cardiac Index (ml / 100 g) Background M ± m 52.98 ± 1.344 14 days lead acetate (40 mg / kg) M ± m 48.56 ± 1.082 p *) Note: (*) - significant (p <0.02) change compared to the background.

Table 3. Indicators of specific peripheral vascular resistance against the background of intragastric administration of lead acetate at a dose of 40 mg / kg (M ± m). Experience Conditions Stat. indicator Specific peripheral vascular resistance (conventional units) Background M ± m 1,547 ± 0,0294 14 days lead acetate (40 mg / kg) M ± m 1.923 ± 0.0288 p *) Note: (*) - significant (p <0.001) change compared to the background.

The proposed method for modeling chronic toxic arterial hypertension and cardiopathy is effective, allows you to study in detail the pathophysiological mechanisms of the toxic effect of heavy metal on the functions of the cardiovascular system and can contribute to the development and search for drugs for the treatment and prevention of chronic toxic arterial hypertension and cardiopathy.

Claims (1)

A method for simulating chronic toxic arterial hypertension and cardiopathy, comprising administering a toxic substance to experimental animals, characterized in that a lead acetate solution is used as a toxic substance, introduced into the stomach once a day at a dose of 40 mg / kg in terms of metal, where a unit of solution equal to 0.2 ml, 8 mg of lead.

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