THE CHANGES OF PULMONARY MICROHEMODYNAMICS IN CASE OF EXPERIMENTAL PULMONRY THROMBOEMBOLISM IN RABBITS AFTER PRETREATMENT WITH CYCLOOXYGENASE-2 INHIBITORS



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Abstract

Background In clinical practice, the problem of reducing pulmonary vascular resistance in case of pulmonary embolism in order to improve right ventricular myocardial contractility remains unsolved. Under these conditions, prostaglandin F2α and thromboxanes A2 and B2 are released by the endothelium, which are factors of pulmonary vascular constriction. Therefore, reducing their synthesis by inhibiting cyclooxygenase type 2 could be a way to influence on constrictor mechanisms.

Aim Study of changes of pulmonary microhemodynamics in modeling pulmonary thromboembolism in rabbits under conditions of using selective cyclooxygenase type 2 inhibitors nimesulide and celecoxib, as well as a water extract of Solanum nigrum (black nightshade) leaves.

Materials and methods The study was performed on perfused isolated lungs of rabbits in situ with stabilization of pulmonary blood flow with measurement of perfusion pressure in the pulmonary artery, determination of capillary hydrostatic resistance and capillary filtration coefficient by volumetry of extracorporeally circulating blood, as well as calculation of pulmonary vascular, pre- and post-capillary resistance.

Results The administration of the cyclooxygenase type 2 inhibitor nimesulide resulted in an increase in pulmonary artery pressure, capillary hydrostatic pressure, pulmonary vascular resistance, and pre- and postcapillary resistance. The treatment of celecoxib, nightshade water extract, and the calcium antagonist diltiazem resulted in a decrease in pulmonary artery pressure, pulmonary vascular and precapillary resistance. Nightshade extract also decreased capillary hydrostatic pressure and postcapillary resistance. During pulmonary artery embolization after pretreatment with indicated above drugs, the increases in pulmonary artery pressure, capillary hydrostatic pressure, and pulmonary vascular resistance, pre- and postcapillary resistance were less than in the control. The changes of the capillary filtration coefficient correlated with the value of the capillary hydrostatic pressure.

Conclusion The dilator effects of celecoxib and black nightshade water extract on pulmonary vessels are due not only to cyclooxygenase-2 inhibition, but also to the blocking effect of these drugs on voltage-dependent Ca2+ channels of smooth muscle cells of the pulmonary vessels. Celecoxib as well as gallic acid, catechin, epicatechin, and quercetin 3-O-glucuronide contained in the black nightshade water extract exhibit properties as L-type Ca2+ channel antagonists. Cyclooxygenase type 2 inhibitors reduce the permeability of the pulmonary vascular endothelium in case of experimental pulmonary thromboembolism. The practical significance of the study consists in the experimental substantiation of the possibility of developing new water-soluble inhibitors of cyclooxygenase type 2 and calcium antagonists based on components of the plant Solanum nigrum (black nightshade).

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About the authors

Vadim Evlakhov

Federal State Budgetary Scientific Institution «Institute of Experimental Medicine», St. Petersburg, Russia;
1-st St. Petersburg Pavlov’s State Medical University, St. Petersburg, Russia.

Author for correspondence.
Email: viespbru@mail.ru
ORCID iD: 0000-0002-2521-8140
SPIN-code: 9072-4077

Docent of physiology, Doctor of Med. Sci., Head of the Department of the Physiology of Visceral System

Russian Federation, 197376, Saint-Petersburg, acad. Pavlov Str., 12

Tatiana Pavlovna Berezina

Federal Budgetary State scientific organization Institute of Experimental medicine

Email: retaber@mail.ru
ORCID iD: 0000-0003-0647-2458

кандидат биологических наук, научный сотрудник  лаборатории физиологии висцеральных систем им. К.М. Быкова 

Russian Federation, 197376, St. Petersburg, acad. Pavlov str., 12

Natalia Anatolievna Pasatetskaya

Federal Budgetary State scientific organization Institute of Experimental medicine

Email: npasatetckaia@yandex.ru
ORCID iD: 0000-0001-8979-6460

Candidate of Biological Sciences, Senior Research Fellow of the Laboratory of the Physiology of Visceral Systems named  acad. K.M. Bykov

Russian Federation, 197376, St. Petersburg, acad. Pavlov st., 12

Aleksey Igorevich Lopatin

Federal Budgetary State scientific organization Institute of Experimental medicine

Email: lopatin.alexey@yandex.ru
ORCID iD: 0009-0003-2746-2088

Junior Research Fellow of the Laboratory of the Physiology of Visceral Systems named  acad. K.M. Bykov

Russian Federation, 197376, St. Petersburg, acad. Pavlov St., 12

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