Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences65156910.31857/S0869813923050035XQKAKUEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИThe Impact of T- and L-Type Calcium Channels Blockers on Pulmonary Microhemodynamics in Experimental Model of Pulmonary ThromboembolismВлияние блокаторов кальциевых каналов T- и L-типа на микрогемодинамику легких при экспериментальной тромбоэмболии легочной артерии у кроликовEvlakhovV. I.ЕвлаховВ. И.viespbru@mail.ruPoyassovI. Z.ПоясовИ. З.viespbru@mail.ruBerezinaT. P.БерезинаТ. П.viespbru@mail.ruInstitute of Experimental MedicineИнститут экспериментальной медицины01052023109564365501022025Copyright ©; 2023, В.И. Евлахов, И.З. Поясов, Т.П. БерезинаCopyright ©; 2023, В.И. Евлахов, И.З. Поясов, Т.П. Березина2023В.И. Евлахов, И.З. Поясов, Т.П. БерезинаВ.И. Евлахов, И.З. Поясов, Т.П. Березинаhttps://journals.eco-vector.com/0869-8139/article/view/651569

In acute experiments on isolated perfused rabbit’s Сhinchilla lungs changes of pulmonary microhemodynamics were studied in case of pulmonary embolization in the comparison group and after pretreatment with ethosuximide, mibefradil, chloroquine and nifedipine. In response to administration of T-type Ca2+-channel blockers ethosuximide and mibefradil, pulmonary artery pressure, precapillary and pulmonary vascular resistance decreased approximately to the same extent, postcapillary resistance did not change. After pretreatment with chloroquine pulmonary artery pressure, precapillary and pulmonary vascular resistance decreased more than in response to the administration of ethosuximide and mibefradil and the antagonist of L-type Ca2+-channels nifedipine; postcapillary resistance decreased. In the case of chloroquine administration combined with infusion of the KATP- channel blocker glibenclamide, most parameters of pulmonary microcirculation decreased almost to the same extent as in response to mibefradil administration, and postcapillary resistance did not change. After pretreatment with chloroquine in response to pulmonary embolization, pulmonary vascular resistance, pre- and postcapillary resistance increased less pronounced than with thromboembolism after pretreatment with ethosuximide, mibefradil and nifedipine. When modeling thromboembolism after pretreatment with chloroquine combined with KATP-channels blocker glibenclamide, the studied hemodynamics parameters increased to the same extent as after nifedipine pretreatment. Thus, chloroquine exhibits the properties of L- and T-type Ca2+-channels blocker, as well as an activator of KATP-channels, whereas ethosuximide has a blocking effect mainly on T-type Ca2+-channels of smooth muscle cells of pulmonary arterial vessels. Shifts of capillary filtration coefficient under these conditions depend more on changes of precapillary resistance than from the changes of permeability of endothelium of pulmonary vessels.

В острых опытах при перфузии изолированных легких кроликов Сhinchilla изучали изменения легочной микрогемодинамики в условиях эмболизации легочной артерии на фоне действия этосуксимида, мибефрадила, хлорохина и нифедипина. В ответ на применение блокаторов Ca2+-каналов T-типа этосуксимида и мибефрадила давление в легочной артерии, прекапиллярное и легочное сосудистое сопротивления уменьшались примерно в равной степени, а посткапиллярное сопротивление не изменялось. В условиях применения хлорохина давление в легочной артерии, прекапиллярное и легочное сосудистое сопротивления снижались больше, чем в ответ на применение этосуксимида и мибефрадила и антагониста Са2+-каналов L-типа нифедипина; посткапиллярное сопротивление уменьшалось. В случае применения хлорохина на фоне инфузии блокатора KATP-каналов глибенкламида большинство показателей легочной микроциркуляции снижалось практически в такой же степени, как и в ответ на применение мибефрадила, а посткапилярное сопротивление не изменялось. На фоне действия хлорохина в ответ на эмболизацию легочной артерии сопротивление сосудов легких, пре- и посткапиллярное сопротивления возрастали менее выражено, чем при тромбоэмболии в условиях применения этосуксимида, мибефрадила и нифедипина. При моделировании тромбоэмболии на фоне применения хлорохина в условиях блокады KATP-каналов глибенкламидом исследуемые гемодинамические показатели увеличивались в такой же степени, как и на фоне действия нифедипина. Таким образом, хлорохин проявляет свойства блокатора Са2+-каналов L- и T-типа, а также активатора KATP-каналов, тогда как этосуксимид оказывает блокирующее влияние преимущественно на Ca2+-каналы T-типа гладкомышечных клеток легочных артериальных сосудов. Сдвиги коэффициента капиллярной фильтрации в указанных условиях в большей степени зависят от изменений прекапиллярного сопротивления, чем от проницаемости эндотелия сосудов легких.

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