Petryk I. Cardioprotective effects of spiro [indole-3,1'-pyrol[3,4-с]pyrol]-5'-(4-methylphenyl)-3'-[2-(methylthio)etyl]-3a',6a'-dihydro-2'H-spiro[indole-3,1'-pyrolo[3,4-c]pyrol]-2,4',6'(1H,3'H,5'H)-trion in front of acute cardiac ischemia and stress cardiomyopathy (experimental study)

The thesis is devoted to solving the actual problem of pharmacology, for increase of efficacy of cardioprotective action in acute coronary syndrome by using 3,2'-spiro-pyrolo-2-oxindole derivate, particularly spiro[indole-3,1'-pyrol[3,4-с]pyrol]-5'-(4-methylphenyl)-3'-[2-(methylthio)etyl]-3a',6a'-dihydro-2'H-spiro[indole-3,1'-pyrolo[3,4-c]pyrol]-2,4',6'(1H,3'H,5'H)-trion, which has a laboratory code compound R-86 and which has a blocking effect on the enzyme 11-β-hydroxysteroid dehydrogenase of the first type and justified the feasibility and possibility of creating a new drug based on it. Using the comprehensive approach for pharmacological screening, it was determined that the compound R-86 in dose of 10 mg/kg administered intragastrically shows the highest cardioprotective activity in the conditions of diathermocoagulatory myocardial necrosis, and adrenaline cardiomyopathy, cardiocerebral dysfunction and myocardial infarction. The multi-vector mechanisms of compound R-86 protective action which is associated with its anti-steroid effect, corrective action on the exchange of nitric oxide, stimulatory effect on coronary blood circulation, elimination of energy deficit and lactate acidosis, which takes place against the background of reduction of lipid peroxidation processes, peptide oxidation modification and activation of its own antioxidant system.