Means for warning of the consequences and complications of induced ischemia of the heart


(57) Abstract:

The invention relates to medicine, particularly cardiology, and can be used for the treatment and prevention of the consequences and complications of ischemia and reperfusion injury of the heart. To achieve this goal apply timogen dose to 3.58-to 1.79 mg/kg intravenously before-induced ischemia. The drug significantly reduced the likelihood of consequences and complications due to ischemia and reperfusion of the heart, contributed to the recovery of cardiac function. 6 Il.

The invention relates to medicine, primarily to cardiology, and can be used to prevent ischemic and postischemic heart damage in humans. It is known that cardiovascular diseases are on the first place among the causes of mortality, with the principal cause of mortality in cardiac patients with coronary heart disease (CHD) and its complications.

Known drug timogen used in the clinic as an immunomodulator. It does not affect the immune system of healthy individuals does not cause toxic reactions in a dose of 10,000 times therapeutic, has no chronic toxicity. When it is oricheskogo Committee of the USSR Ministry of health to medical application dated January 13, 1989/. L. 1989, C. 10). The authors examined the antiischemic properties of the drug, allowing you to use it for a new purpose.

Currently there are many different drugs used for the prevention and treatment of coronary heart disease.

However, they all have significant side effects.

The purpose of the invention is the prevention of complications and consequences of ischemia and repartie heart without side effects.

To achieve this goal was to use the drug timogen dose 7,15 µg/kg, This dose was the most effective in the treatment of cardiac arrhythmias, and, as you know, the arrhythmia is one of the most dangerous complications of ischemic heart disease.

The invention is illustrated in Fig. 1-6.

Example 1. A control series of 8 animals.

The rat was scored under light ether anesthesia. Perfusion of the heart was carried out through the aorta using Langendorf solution of the following composition: 150 mM NaCl, 5 mM KCl, 2 mM NaHCO3, 1 mM MgCl2, 2.5 mM CaCl2, 2 mM Tris-HCl (pH 7,4), 11 mM glucose. The solution was saturated with oxygen and heated to 37oC. To simulate ischemia and reperfusion on 20 min off the original solution and then perfesional heart normal solution Hears D. Y et al. Protection of the ischemic myocardium; cardioplegia.-N. Y, Raien Press. -1 is eskay contracture (for this purpose, registered diastolic pressure in the left ventricle), during reperfusion development reperfusion contracture, reconstruction of the amplitude of contractions (including that of the amplitude of at least 50% from baseline), the output of myoglobin, actinolite (adenosine+inosine+hypoxanthine), pyridine nucleotide (NADH+NADPH).

In the control reperfusion arrhythmias was observed in 100% of cases, including ventricular fibrillation in 37.5% of the amplitude of the heartbeat was restored 12.5% (Fig. 1). The overall picture of the dynamics of the amplitude of the contractions shown in Fig. 2.

Example 2. Series with timagenes 8 animals.

Conditions experience was different in that for 5 minutes before doing ischemia heart was perfesional solution containing timogen at a concentration of 0.3 μm, which corresponds to the dose of the drug 7,15 ág/kg

On the model of ischemia and reperfusion, the drug significantly reduced the number of reperfusion arrhythmias (from 100% to 16.6%), completely prevented the development of ventricular fibrillation (Fig. 1); contributed to the restoration force of myocardial contractions (control of 12.5% in the experience of 100% (Fig. 1, 2), prevented the development of ischemic contracture (Fig. 3). During reperfusion, the drug prevented the increase in diastolic pressure in the left ventricle (Fig. 3), reduced the release into the flowing perf.

Example 3. Series with verapamil 8 animals.

Conditions of experience differed from the control by the fact that for 5 minutes before playing ischemia heart was perfesional solution containing verapamil at a concentration of 0.2 μm (Hears D. Y. et al. Protection of ischemic myocardium: cardioplegia. N. Y. 1981, P. 73-79).

Reperfusion arrhythmias was observed in 87.5% of cases, in the remaining 12.5% of the heart is not restored contractile activity. Fibrillation verapamil prevented completely. From developed arrhythmias 12.5% over asistoliei, i.e., the total number of hearts with zero amplitude of contractions was 25% (Fig. 1). The amplitude of contractions was not restored to the initial level (Fig. 2).

Verapamil reduced the degree of ischemic contracture, but had little impact on reperfusion (Fig. 3).

The drug reduced the release of pyridine nucleotides (Fig. 5), but increased the output Danilovich (Fig. 4) and significantly increased the release of myoglobin (Fig. 6) compared with the control, i.e., he increased the depth of cytolysis.

Thus, timogen limited the severity of the complications and consequences of induced ischemia and reperfusion of the heart, making it more effective than verapamil.

Using this method, you can prevent arrhythmia b induced in the experiment ischemia of the heart.


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