MODIFICATION OF ALVEOLOCAPILLARY PERMEABILITY BY NEBULIZED HEPARIN IN RAT’S MODEL OF VENTILATOR INDUCED LUNG INJURY

Reshetnyak N. А., Yakubenko O. D., Khripachenko I. А.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

The aim of the study was to determine influence on the alveolocapillary membrane permeability in condition of ventilator induced lung injury experimental model. Experiments were performed on the ten Wistar laboratory male rats (180-240 g of BM). Rats expose to pretreatment of nebulized heparin in the dose, which calculated as 200 U/kg of animal BM, by aerosol chamber Cirrus 2 Intersurgical, ltd, (UK). In the first group ventilator induced lung injury we simulate by mechanical ventilation with tidal volume of 20 ml/kg (moderate volumotrauma), and in second group of rats with tidal volume of 40 ml/kg (severe volumotrauma). After mechanical ventilation completion, the animals withdraw from experiment and by bronchoalveolar lavage; selection of bronchoalveolar liquid probe was performed on the open lungs. In the bronchoalveolar liquid, we determine concentration of total protein according to Lowry with bovine serum albumin as standard and urea concentration by urease method. In addition we determine level of dien conjugates according to method of Gavrilova and all, catalase activity according to Koroluk and all method and content of middle molecular mass substances by extinction at 238 nm., 254 nm., 260 nm., and 280 nm. of wavelength according to Gabrielyan. Serum concentration of the urea we used for determination of true concentration of analyzing substances in bronchoalveolar liquid with accounting of dilution by the bronchoalveolar lavage solution. We found that pretreatment of rats with nebulized heparin in the dose of 200 U/kg of animals BM in condition of moderate lung volumotrauma practically not change alveolocapillary permeability for total protein and middle molecular mass substances. The level of lipoperoxidation was not changed in the response to pretreatment with nebulized heparin but bronchoalveolar liquid catalase activity significantly increased. We also found that pretreatment of rats with nebulized heparin in condition of severe lung volumotrauma characterized by near sevenfold decreasing of total protein concentration, and more than twofold decreasing middle molecular mass substances, with determined by extinction at 238 nm wavelength, and near 14 fold decreasing of bronchoalveolar liquid dien conjugates content. Thereby, nebulized heparin in condition of experimental model of ventilator induced lung injury with moderate volumotrauma not change alveolocapillary membrane permeability for total protein and middle molecular mass substances but has protective effect concerning severe volumotruma. This one probably determined by finding decreasing level of lipoperoxidation in bronchoalveolar liquid. The finding may be useful in respect to possibility of clinical trials and nebulized heparin using effectiveness estimation in the prevention of ventilator induced lung injury in risk group patients.

nebulized heparin, ventilator induced lung injury model, rats

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«Bulletin of problems biology and medicine» Issue 1 part 1 (126), 2016 year, 199-203 pages, index UDK 616.16+616.24:612.221.3+615.273.53] - 001+615.816