Aim. To test the new selenium containing metal complex (Zn2+) compounds by acute hypoxia-hypercapnia method in experiments on mice for antihypoxic effect finding. Methods. The screening of antihypoxants in experiments on mice placed in acute hypoxia-hypercapnia condition (AH + H) among 11 new metal complex selenium containing compounds have been performed. Condition of AH + H in animals was formed by their placing in hermetic glass boxes with 0.25 L free volume. Each substance has been used once by intraperitoneal introduction 60 min. before mice placing in AH + H area in doses 10, 25, and 50 mg/kg. The “life span” parameter was used as a criterion of antihypoxic activity. At the definite steps of investigation all animals where undergone to rectal temperature measuring. Results. The antihypoxic effect was shown by 4 compounds among 11 (πQ2719, πQ2720, πQ2721, πQ2882). The greatest result in life span was found in substance πQ2721. In this case the right positive interaction between doses of substances and results was marked - doses 10, 25 and 50 mg/kg provide life span enlargements to 25.1, 81.7 (р < 0.05), and 186.1% (р < 0.005) in comparison with control groups correspondently. The efficiency of etalon substance πQ1983 was near to that of πQ2721 but in dose 50 mg/kg it becomes weaker in activity than new compound. Conclusion. The test resultant of 11 new metal complex (Zn2+) substance with selenium in structure of ligand in use of acute hypoxia-hypercapnia method shows the πQ2721 as an antihypoxant that was confirmed by significant mice life span enlargement after doses 25 and 50 mg/kg during its action that according with dose-dependent rectal temperature decrease. (For citation: Yevseyev AV, Surmenev DV, Parfenov EA, et al. Testing of new selenium containing metal complex compounds by acute hypoxia-hypercapnia method. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(4):46-52. doi: 10.17816/RCF15446-52).

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We studied the effects of complex N-acetyl-L-cysteine compounds with transitional biometals on the inflammatory and adaptation reactions. Some compounds were superior to known antihypoxants and actoprotectors and exhibited significant antiinflammatory activity.

Проанализированы результаты исследований кардиотоксичности противомикробных лекарственных средств. Показано, что антибиотики-макролиды, а также фторхинолоны и некоторые противогрибковые лекарственные средства в определенных условиях могут удлинять интервал QT на ЭКГ. Это является серьезной нежелательной реакцией, способной привести к развитию сердечных аритмий (torsade de pointes) и внезапной смерти пациента. Описаны механизмы аритмогенного действия препаратов. Выявлены основные факторы риска кардиотоксичности: взаимодействие с другими лекарственными средствами, удлиняющими интервал QT, женский пол, пожилой возраст, сопутствующие заболевания сердца, генетическая предрасположенность, гипергликемия, гипотиреоз, электролитные нарушения. Для предупреждения развития кардиотоксических эффектов при назначении противомикробных лекарственных средств необходимо минимизировать факторы риска и проводить мониторинг показателей кардиотоксичности. Следует тщательно подходить к выбору и дозированию препаратов, осуществлять контроль ЭКГ и электролитного баланса крови. При комбинированной фармакотерапии следует прогнозировать возможные фармакодинамические и фармакокинетические взаимодействия, способные усилить аритмогенное действие противомикробных лекарственных средств. Для снижения кардиотоксичности возможно использование метаболических кардиопротекторов, особенно у пациентов с ишемическими поражениями сердца.

The problem of infectious endocarditis currently deserves special attention. According to the data, intrahospital mortality caused by this pathology reaches 20%, which is largely due to the development of potential complications, the most common among which are the development and progression of heart failure, as well as thromboembolic manifestations with the damage to target organs of various localization. The article presents the results of a multicenter study establishing the features of antimicrobial therapy in patients with infectious endocarditis under the conditions of the dominance of gram-positive microorganisms in the etiological structure in the Russian Federation. 440 cases of definite and probable infectious endocarditis in the period from September 2006 to December 2020 were analyzed.