Tool that improves blood flow and myocardial metabolism

 

The invention relates to medicine. The proposed use of mixed agonist of cannabinoid receptors HU-210 as a new vehicle, which improves blood flow and myocardial metabolism. The invention expands the Arsenal of tools specified destination. table 1.

The invention relates to the section of experimental medicine and can be used to create a new effective way of improving blood flow and myocardial metabolism.

Today it is known that HU-210 has cardiovascular [6] and antinociceptive [4] effects, and also has a modulating effect on intracellular signaling systems [4].

We used the means of HU-210 was synthesized in the company Tocris Cookson Ltd. Bristol, U. K.

In its structure this compound ones nature of the following composition: ((6aR)-trans-3-(1,1-Dimethylheptyl)-6a, 7, 10, 10a- - tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol) [4].

We first identified its positive effect on blood flow and myocardial metabolism, leading to smaller area of ischemic necrosis.

It is known that cannabinoids can inhibit the synthesis of camp in the myocardium [3]. A similar effect propranolol able og aritmicheskoy activity of HU-210 on the model adrenal arrhythmias, which proves that antiadrainergicakimi activity of the investigated cannabinoid, comparable with the effect of propranolol [2]. Based on the above, we hypothesized that mixed cannabinoid receptor HU-210 is able to exert a cardioprotective effect. Therefore, we conducted a study of the effect of HU-210 on the size of the area of ischemic necrosis of the myocardium.

The invention will be clear from the following description.

Experiments conducted on rats male Wistar rats weighing 180-200 g Acute myocardial infarction caused by ligation of the left coronary artery for 45 min with subsequent restoration of coronary blood flow during 120 min [5]. In this case, rats were narcoticyou barbarian at a dose of 60 mg/kg intravenously. During the operation the animals were housed under conditions of artificial ventilation. After 2 hours of reperfusion, in order to identify areas of hypoperfusion of the left coronary artery newly bandaged and intravenous bolus was injected 10% solution of the dye Patent blue violet (Sigma) at a dose of 40 mg/kg Then the heart was removed and divided into 6-8 transverse slices with a thickness of 1-1 .5 mm Intact myocardium was separated from risk zones and weighed. The remainder of the muscle tissue was subjected to further coherent buffer (pH 7.4) at a temperature of 37oC. After a 15-minute staining was visually divided nekrotizirovannye myocardium and the area of hypoperfusion with subsequent weighting [5].

HU-210 was dissolved ex tempore in the mixture: ethanol:Cremaphore EL:0.9% NaCl solution in the ratio 1:1:18 and injected intravenously 15 min before ligation of the coronary artery. Control was a group of animals who before coronariography injected with a solvent consisting of a mixture of: ethanol:Cremaphore EL: 0.9% NaCl solution in the ratio 1:1:18. The results obtained were processed statistically using t-test Student.

Example. The study of the cardioprotective activity of HU-210 was conducted according to the following scheme. In the group of experimental animals we have taken 14 rats, which for 15 min before ligation of the left coronary artery was injected intravenously and a solution of the drug. As a control group took 18 animals, which for 15 min before ischemia was intravenously injected solvent not containing HU-210.

After 45 minutes of coronarography and subsequent 2-hour reperfusion, more than half of the total mass of the left ventricle was in a state of hypoperfusion (see table), it is not abrasives after ligation of the coronary artery. In the control group of animals the size of necrosis was (5across 15 minutes before coronariography slightly reduced the size of the zone of hypoperfusion and resulted in a significant decrease (P<0.001) and the size of the zone of necrosis by 44% compared to control values by absolute value and 37% percentage of the area of the infarct zone of hypoperfusion (see table).

Our results indicate that mixed cannabinoid receptor HU-210 by improving blood flow and myocardial metabolism contributes to the limitation of the size of the area of ischemic necrosis in the conditions of the 45-minute coronariography and subsequent 2-hour reperfusion. Thus, this cannabinoid can be used as a new tool that improves blood flow and myocardial metabolism.

LITERATURE 1. Jennings, R. B., Reimer, K. A. Materials of the 2nd Soviet-American Symposium, may 28-30, 1975, Sochi - M.: Medicine, 1977, S. 90-108.

2. Ugdyzhekova D. C., Maimeskul L. A., Y. Davydov, Cannabinoid HU-210 increases the resistance of the heart to the arrhythmogenic effects of epinephrine and aconitine. Bulletin of Arrhythmology. 2000, No. 19, S. 68-71.

3. Li D. M. F., Ng, C. K. M. Effects of tetrahydrocannabinol on the adenylate cyclase activity in ventricular tissue of the rat heart. Clin. Exp. Pharmacol. Physiol. 1984; 11(1): 81-85.

4. Pertwee R. G. Pharmacology of cannabinoid chemistry receptor ligands. Curren Med. Chem. 1999; 6: 2085-2093.

5. Schultz J. E. J., Hsu, A. K., Nagase H., Gross G. J. TAN-67,1-opioid receptor agonist, reduces infarct dementia size via activation of Gi/oproteins and KATPchanels. Am. J. Phisiol. 1998; 274: H909-H914.

6. Vidrio H., Sanchez-Salvatori, M. A., Medina, M. Cardiovascular effects of (-)-11-OH-8-tetrahydrocannabinol-dimethylheptyl in rats. J. Cardiovascular. Pharmacol. 1996; 28: 332-33 the Directors HU-210 as a new vehicle, improves blood flow and myocardial metabolism.

 

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1 cl, 1 tbl, 2 ex

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