Abstract
Objective. To investigate the possibility of pharmacological correction of acute lung injury of aspiration genesis with a liposomal form of dexamethasone in experiment. Materials and methods. For the experiment, simple liposomes were prepared from phosphatidylcholine and cholesterol with an average size of 320±50 nm and a dexamethasone concentration of 2.98±0.02 mg/ml. The study used outbred white rats, divided into four groups of 16 animals. 1st group Control (without experimental therapy), 2nd group - Experiment 1, where a solution of dexamethasone was injected intravenously at a dose of 6 mg/kg, 3rd group - Experiment 2, where an intravenous combination of dexamethasone solution (6 mg/kg) and hypertonic (7.5%) NaCl solution was administered once, and group 4 - Experiment 3, where liposomes with dexamethasone (6 mg/kg) were injected intravenously once in hypertensive (7.5%) NaCl solution. The main functional parameters of the animals (heart rate, blood pressure, saturation of hemoglobin with oxygen, partial pressure of blood oxygen and respiration rate) were subject to analysis. Functional parameters were analyzed before modeling acute lung injury and after 5 min, 1, 4, 24 hours, and 6 days. At the end of the experiment (day 6) the degree of pulmonary edema and histological signs of acute lung injury were assessed. Morphology was assessed quantitatively in each group. Results. The study found that liposomal dexamethasone in hypertonic NaCl solution, when administered intravenously, was more effective than aqueous dexamethasone solution in correcting functional impairment in acute lung injury. The combination of hypertonic sodium chloride solution with dexamethasone more markedly increases blood pressure and reduces the degree of pulmonary oedema. In acidine pepsin aspiration, liposomal dexamethasone in hypertonic NaCl solution most effectively increased animal survival. Conclusion. Compared with dexamethasone in hypertonic NaCl solution, liposomal dexamethasone is more effective in increasing animal survival and protecting lung tissue from aspiration damage by acidine pepsin.
Highlights
Simple liposomes were prepared from phosphatidylcholine and cholesterol with an average size of 320±50 nm and a dexamethasone concentration of 2.98±0.02 mg/ml
The study used outbred white rats, divided into four groups of 16 animals. 1st group Control, 2nd group – Experiment 1, where a solution of dexamethasone was injected intravenously at a dose of 6 mg/kg, 3rd group – Experiment 2, where an intravenous combination of dexamethasone solution (6 mg/kg) and hypertonic (7.5%) NaCl solution was administered once, and group 4 – Experiment 3, where liposomes with dexamethasone (6 mg/kg) were injected intravenously once in hypertensive (7.5%) NaCl solution
Functional parameters were analyzed before modeling acute lung injury and after 5 min, 1, 4, 24 hours, and 6 days
Summary
Густую дисперсию липосом доводили до объема 5 мл 7,5% раствором NaCl. Концентрацию дексаметазона в липосомах определяли спектрофотометрически при λ = 241 нм. ОПЛ моделировали путем введения в трахею 0,03 мл раствора ацидин-пепсина. Средство для наркоза вводили за 20 минут до моделирования ОПЛ в дозе, исходя из массы тела животного. Всем животным после моделирования ОПЛ и окончания регистрации функциональных показателей с целью профилактики инфекционных осложнений вводили цефтриаксон (порошок во флаконах, 1 г, ОАО «Биосинтез», Россия) в дозе 200 мг/кг внутримышечно в область бедра 1 раз в сутки в течение 6 дней Анализ степени легочного отека производили после забоя животных на 6-е сутки эксперимента. Для оценки степени повреждения каждой из долей легкого использовался гистологический срез, характеризующийся максимальными признаками повреждения. Для всех статистических процедур в данном исследовании уровень значимости p был равным 0,05
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