12+

STUDY OF DOSE-DEPENDENT EFFECT OF 2-ETHYL-6-METHYL-3 HYDROXYPYRIDINE SUCCINATE ON THE CONTRACTILE FUNCTION OF ISOLATED RAT HEART

In experiments on the isolated rat heart there were studied the effects of different doses (21.43 mg/kg/day and 85.72 mg/kg/day) 2-ethyl-6-methyl-3 hydroxypyridine succinate ("EkoPharmInvest", Russia), on the contractile function of isolated hearts subjected to prior doxorubicin model (20 mg/kg, intraperitoneal) of pathology. The dynamic of the power mechanisms of ion transport was evaluated by imposing high heart rate (480 BPM) and increase concentration of Са2+ to 5 mmol in perfusate. The results indicate that Mexicor at the dose of 21.43 mg/kg/day does not provide a cardioprotective effect in this model of pathology. Mexicor has the cardioprotective effect at the dose of 85.72 mg/kg/day in relation to the isolated heart, that is resulted in the recovery of the contractile function of the heart and reducing the "diastole defect" (SТТI).

Figures

Table 1. Indices of contractile function of the rat hearts (M±m; n=8) . The concentration of Ca2+ in perfusate is 2.5 mmol

Table 2. Indices of contractile function of the rat hearts (M±m; n=8). The concentration of Ca2+ in perfusate is 5 mmol, stimulation by electrical impulses (480 BPM)

 

 

Figure 1a Exercise tolerance test with submaximal electrical stimulation of a rat heart isolated by Langendorf. 

Pressure profile within the left ventricle (Mmhg) at imposing qickened heartbeat (480 bpm) within 15 sec. Са2+ concentration in perfusate – 5 mmol/L. Intact group.

 

 

Figure 1b Exercise tolerance test with submaximal electrical stimulation of a rat heart with doxorubicin myocardiopathy. 

Pressure profile within the left ventricle (Mmhg) at imposing qickened heartbeat (480 bpm) within 15 sec. Са2+ concentration in perfusate – 5 mmol/L. Doxorubicin (20 mpg) given at a single dose within 48 hours.

 

 

Figure 2a Interaction of Mexicor (21,43 mg/kg/d) on the results of exercise tolerance test with submaximal electrical stimulation of a rat heart isolated by Langendorf with doxorubicin myocardiopathy.
Pressure profile within the left ventricle (Mmhg) at imposing qickened heartbeat (480 bpm) within 15 sec. Са2+ concentration in perfusate – 5 mmol/L. Doxorubicin (20 mpg) given at a single dose within 48 hours.
 

 

 

Figure 2b Interaction of Mexicor (85,72 mg/kg/d) on the results of exercise tolerance test with submaximal electrical stimulation of a rat heart isolated by Langendorf with doxorubicin myocardiopathy.
Pressure profile within the left ventricle (Mmhg) at imposing qickened heartbeat (480 bpm) within 15 sec. Са2+ concentration in perfusate – 5  mmol/L. Doxorubicin (20 mpg) given at a single dose within 48 hours.
 

Figure 3. The influence of Mexicor (21.43 mg/kg/day, 85.7 mg/kg/day) on the SТТI, cu (under doxorubicin-induced cardiomyopathy).

Comment: * - р<0.05 in comparison with intact animals; ** - р<0.05 in comparison with control group.

Figure 4. Diagramming of the main ways of action of doxorubicin and iron, which catalyzes the oxidative stress leading to cardiomyopathy and the application points of Mexicor.

Comment: Fe – iron, FAD/FADH2 – flavoprotein, GSH – reduced glutathione, GSSG – oxidized glutathione, H2O2 – hydrogen peroxide, NAD(PH)+ – nicotinamide adenine dinucleotide (phosphate), O2- – superoxide anion, OH – hydroxyl radical, SOD – superoxide dismutase.

DOI: DOI: 10.18413/2500-235X-2017-3-1-3-9
Number of views: 1626 (view statistics)
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