Shaposhnikova Y. Cellular and humoral mechanisms of development of tolerance to organic nitrates in patients with ischemic heart disease.

Object of investigation: patients with ischaemic heart disease and stable angina of effort of the ІІІ functional class. Methods of investigation. Determination of the effective single ISDN dose - with pair veloergometry (bicycle ergometer "Seca - Cardiotest"). Evaluation of individual sensitivity to antiaggregatory effect on the platelet model in vitro - aggregation analyzer "Universal aggregometer". Plasma and platelet cAMP and cGMP levels and plasma endothelin-1 level - immune-enzyme assay (device for immune-enzyme analysis "Multiscan"); blood lipid spectra investigation - device for immune-enzyme analysis "Multiscan"; lipid peroxidation intensity according to the TBA-active products level - spectrophotometric analysis (photoelectric photometer КФК-3); NO2 level - spectrophotometric analysis with Griss reaction (spectrophotometer СФ-26); whole blood SH-groups - calorimetric method with Ellman reagent (multichannel microphotometer "Flow"). Echocardiographic investigation - apparatus "Aloka SSD-280" (Japan). The obtained data mathematical analysis - PC of "Pentium-II" type. Theoretical novelty: On the basis of peculiarities of vasoconstrictor and vasodilator systems' changes in patients with the progressive tolerance and sufficient sensitivity to the organic nitrates therapy, possible mechanisms of tolerance development are identified. Humoral and cellular indices, associated with the organic nitrates substitutive therapy sensitivity, are revealed. It is proved, that endothelial functional activity determines both organic nitrates therapy effectiveness and risk of the tolerance phenomenon development. Practical novelty: Predictive criteria of organic nitrate tolerance development are worked out on the basis of analysis of endothelial functional state and platelet haemostasis activity, enabling the reliable evaluation of ON substitutive therapy effectiveness and its timely correction. On the basis of the revealed humoral changes, promoting the nitrates tolerance development, different schemes of ONadministration are studied, and comparative assessment of their effectiveness in relation to the tolerance phenomenon prevention is carried out. The degree of introduction: Methodical recommendations for optimization of antianginal therapy with prolonged nitrates with account of individual sensitivity to therapy are worked out, which are supported with 2 patents for invention of Ukraine. Utilization field: The work relates to the field of cardiology; the results can be introduced, with the aim of increase of organic nitrates antianginal therapy effectiveness in patients with IHD, on all levels of medical care provision - rural, regional, municipal health care institutions, as well as they can be used in the and scientific researches.