Lynnyk O. Transfusion correction of endothelial dysfunction and development of inflammatory response in the surgical treatment of burn wounds

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0823U101517

Applicant for

Specialization

  • 222 - Медицина

Specialized Academic Board

ДФ 26.613.152

Shupyk National Healthcare University of Ukraine

Essay

The dissertation provides a theoretical justification and solution to the current problem, which consists in increasing the effectiveness of treatment of burn patients by developing and implementing schemes for transfusion correction of endothelial dysfunction and indicators of inflammation during surgical treatment of burn wounds. The study included the results of the examination and treatment of 71 patients with burn lesions ranging from 10 to 60% of the total body surface area (TBSA), aged from 24 to 65 years. All patients were divided into two groups - the main group and the comparison group. The main group included 49 patients with thermal burns with TBSA from 10 to 60%, who, in addition to the standard scheme of transfusion therapy and surgical treatment, were treated with endotheliotropic, antiproteolytic and antioxidant drugs. Depending on the additional drug used in transfusion therapy schemes, the patients of the main group were divided into three subgroups. Subgroup 1 included 23 patients who were treated with an endotheliotropic drug – L-carnitine and arginine hydrochloride in the transfusion therapy scheme during surgical treatment, subgroup 2 - 12 patients who were treated with a proteinase inhibitor drug - ulinastatin, and subgroup 3 - 14 patients who were treated with an antioxidant drug - ethylmethylhydroxypyridine succinate. The comparison group included 22 patients who underwent a standard generally accepted scheme of transfusion therapy and surgical treatment without additional drugs. The results of endotheliotropic, antiproteolytic and antioxidant drugs usage were studied according to the dynamics of changes indicators of endothelial dysfunction, indicators of pro- and anti-inflammatory cytokines, proteolytic activity indicators and cells phagocytic activity in peripheral blood and capillary blood of the thermal injury zone 9 in patients of each subgroup of the main group and in patients of the comparison group. Morphological and immunohistochemical confirmation was conducted based on markers of angiogenesis activation, epidermization, and epithelialization. Clinical success criteria for surgical treatment included: reduction in the area of excisions and wound closure, the timing of the first autodermoplasty, the timing of complete final wound closure, the number of surgical interventions, the frequency of infectious and inflammatory complications, and the duration of the patient's hospital stay. It was observed that on the 2nd to 3rd day after burn trauma, there was an increase in the levels of markers of endothelial dysfunction, namely endothelin-1 (ET-1) and homocysteine, in the capillary blood of the wound and peripheral blood. The levels of ET-1 in the blood from the burn wound exceeded those in peripheral blood, indicating a prevalence of local vasoconstriction in the burn area, which significantly affected the development of the wound healing process and the timing of surgical treatment. When studying the dynamics of changes in nitric oxide (NO) indicators in the capillary blood of the burn wound, it was found that in both groups on the 2nd to 3rd day after the burn, the levels of NO metabolites exceeded reference values. However, on the 7th to 8th day, in the capillary blood of the wound in patients from the comparison group, the NO level was 3.48±0.2 µmol/L, significantly lower than both the initial levels (8.68±0.08 µmol/L) and reference values (4.69±0.42 µmol/L) (p<0.05). This indicated a decrease in NO bioavailability, its inactivation by active oxygen species, insufficient substrate for eNOS, leading to the exacerbation of endothelial dysfunction and a prevalence of vasospasm in the burn wound area. It was determined that the application of the elaborated transfusion therapy regimens in the early period of burn disease led to a significant reduction in the levels of the vasoconstrictor factor ET-1 in the blood and a significant decrease in homocysteine levels, especially in the capillary blood of the burn wound. This indicated a reduction in cytotoxic effects on the endothelium. The use of the proposed transfusion therapy allowed maintaining NO levels on the 7th to 8th day at twice the level of the comparison group, both through the provision of NO substrate and through the use of S-nitrothiols for NO synthesis.

Research papers

Козинець Г.П., Осадча О. І., Линник О. М., Шматова О. О. Вплив препаратів ендотеліотропної дії на показники ранового процесу у хворих з опіками. Modern Medical Technology. 2018;4(39):14-18. https://zmapo-journal.com/downloads/archive/2018-4.pdf

Козинець Г. П., Осадча О. І., Коваленко О. М., Линник О. М. Вплив ранового процесу на формування системної запальної відповіді та раннього сепсису у хворих з опіками в гострому періоді опікової хвороби. Modern Medical Technology. 2019 Aug;2(41)part 3:13-20. https://zmapo-journal.com/index.php/journal/issue/view/4/2-41-2019-3-pdf

Линник О.М., Осадча О.І., Козинець Г.П., Янчій І.Р., Шматова О.О., Боярська Г.М. Особливості формування імунної відповіді на термічну травму. Fiziol. Zh. 2021; 67(6): 32-39 DOI: 10.15407/fz67.06.032 https://fz.kiev.ua/journals/2021_V.67/6/2021-6-32-39.pdf

Линник О.М., Козинець Г.П., Осадча О.І. Результати застосування препарату інгібітора протеаз у пацієнтів в гострому періоді опікової хвороби/ Modern Medical Technology. 2022 Mar;1(52):56-61. DOI: 10.34287/MMT.1(52).2022.10 https://zmapo-journal.com/index.php/journal/article/view/180/177

Козинець Г.П., Осадча О.І., Линник О.М., Жернов О.А. Особливості формування системної запальної відповіді у пацієнтів у гострий період опікової хвороби. Український медичний часопис. 2022 May;3(149):61-65. DOI: 10.32471/umj.1680-3051.149.229080 https://api.umj.com.ua/wp/wp-content/uploads/2022/05/5112.pdf

Коваленко О.М., Осадча О.І., Коваленко А.О., Гриша А.С., Линник О.М., Белінська Н.Г. Особливості лікування сепсису у хворих з опіковою хворобою. Perioperaciina Medicina. 2020 June;3(1):14-20. DOI: 10.31636/prmd.v3i1.3 https://perioperative.org.ua/index.php/prtmdc/article/view/39/38

Линник О.М., Козинець Г.П. Застосування етилметилгідроксипіридину сукцинату у пацієнтів з опіками. The Ukrainian Journal of Clinical Surgery. 2023 March/April; 90(2):29-33 DOI:10.26779/2786-832X.2023.2.29 https://hirurgiya.com.ua/index.php/journal/article/view/1090/1069

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