Cardioprotective efficiency of pharmacological postconditioning using lactic acid in ischemia-reperfusion of the myocardium in rats with transitional hypercholesterolemia

Чепелев, С. Н.; Висмонт, Ф. И.; Gubkin, S. V.; Маслов, Л Н

doi:10.29235/1814-6023-2021-18-2-135-146

Cited by 4 publications

(1 citation statement)

References 23 publications

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“…Жизнеспособный миокард (клетки, сохранившие дегидрогеназную активность) окрашивался в кирпично-красный цвет, а некротизированная ткань была бледно-желтой. При помощи компьютерной планиметрии и взвешивания срезов миокарда левого желудочка определяли соотношение зоны инфаркта и зоны риска [4]. Молодые крысы, которым моделировали И/Р миокарда, а также на 25-й мин реперфузии вводили в левую общую яремную вену физ.…”

Section: методикаunclassified

Participation of L-lactate in the cardioprotective effect of remote ischemic postconditioning in young and old rats

Чепелев,

Висмонт,

Губкин

2023

Zhurnal «Patologicheskaia Fiziologiia I Eksperimental`naia Terapiia»

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Введение. Разработка новых эффективных методов предотвращения или ослабления ишемического и реперфузионного повреждения миокарда и выяснение механизмов их реализации является актуальной задачей современной экспериментальной и клинической медицины. Дистантное ишемическое посткондиционирование (ДИПост) является многообещающим неинвазивным методом, способным эффективно и безопасно уменьшить размер инфаркта миокарда. Цель исследования – выяснение участия L-лактата в реализации инфаркт-лимитирующего эффекта ДИПост у молодых и старых крыс. Методика. Исследование участия L-лактата в реализации кардиопротекторного эффекта ДИПост при ишемии-реперфузии (И/Р) миокарда выполнено на 120 нелинейных белых крысах-самцах: 60 молодых крыс (масса 200-240 г, возраст 4±1 мес), и 60 старых крыс, (масса 400-450 г, возраст 24±1 мес). Для моделирования инфаркта миокарда осуществляли коронароокклюзию (30 мин) и реперфузию (2 ч). Оценивали размер зоны некроза и зоны риска. ДИПост моделировали путем 15-минутного наложения зажимов на задние конечности через 10 мин после начала реперфузии. У животных определяли уровень L-лактата в плазме крови в модели ДИПост (15-минутное пережатие обеих бедренных артерий через 10 мин после 30-минутной острой коронароокклюзии). Посткондиционирование с помощью L-лактата (ПостЛ) осуществлялось путем введения в левую общую яремную вену раствора L-лактата (10 мг/кг) через 25 мин после начала репефузии. Результаты. У молодых и старых крыс после 15-минутного пережатия обеих бедренных артерий, вызывающего ДИПост, отмечалось повышение уровня L-лактата в плазме крови в 2,28 и 2,34 раза, соответственно. Размер зоны некроза в исследуемых группах был следующим: И/Рмолодые составил 45±4, И/Рстарые – 47±5, ДИПостмолодые – 25±3 (p<0,001), ДИПостстарые – 28±3 (p<0,001), И/Р+Физ.р-рмолодые – 45±6, И/Р+Физ.р-рстарые – 48±6, ПостЛмолодые – 33±3 (p<0,01) и ПостЛстарые – 35±4% (p<0,01). Заключение. Установлено, что ДИПост оказывает инфаркт-лимитирующий эффект и сопровождается повышением уровня L-лактата в плазме крови. Выявлено, что ПостЛ приводит к снижению размеров зоны некроза в миокарде левого желудочка у молодых и старых крыс на 26,7 и 25,5% соответственно. Background. The development of new effective methods for preventing or mitigating ischemic and reperfusion injury to the myocardium and elucidating their mechanisms is an urgent task of modern experimental and clinical medicine. Remote ischemic postconditioning (RIPost) is a promising non-invasive method that can effectively and safely reduce the size of myocardial infarction. The aim of the study was to elucidate the involvement of L-lactate in the infarct-limiting effect of RIPost in young and old rats. Methods. The study of the participation of L-lactate in the realization of the cardioprotective effect of RIPost in ischemia-reperfusion (I/R) of the myocardium was performed on 120 mongrel white male rats (60 young rats weighing 200-240 g and aged 4±1 months and 60 old rats weighing 400-450 g and aged 24±1 months). Coronary occlusion (30 min) and reperfusion (2 h) were performed to model myocardial infarction. The necrotic zone area and area at risk were measured. RIPost was modeled by clamping the hind limbs for 15 minutes 10 minutes after the start of reperfusion. The concentration of L-lactate in blood plasma was measured in the RIPost model (by 15-minute ischemia of both femoral arteries 10 min after 30-minute acute coronary occlusion). Postconditioning with L-lactate (PostL) was produced by injecting L-lactate 10 mg/kg into the left common jugular vein 25 minutes after the start of reperfusion. Results. In young and old rats, after the 15-minute clamping of both femoral arteries during RIPost, blood plasma concentrations of L-lactate increased 2.28 and 2.34 times, respectively. The sizes of the necrotic zone in the studied groups were as follows: I/Ryoung was 45±4, I/Rold, 47±5, RIPostyoung, 25±3 (p<0,001), RIPostold, 28±3 (p<0,001), I/R+Salineyoung – 45±6, I/R+Salineold – 48±6, PostLyoung, 33±3 (p<0,01), and PostLold, 35±4% (p<0,01). Conclusions. RIPost has an infarction-limiting effect and is accompanied by an increase in the blood plasma concentration of L-lactate. It was found that PostL leads to a decrease in the size of the necrosis zone in the myocardium of the left ventricle in young and old rats by 26.7 and 25.5%, respectively.

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Section: методикаunclassified

Participation of L-lactate in the cardioprotective effect of remote ischemic postconditioning in young and old rats

Чепелев,

Висмонт,

Губкин

2023

Zhurnal «Patologicheskaia Fiziologiia I Eksperimental`naia Terapiia»

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Myocardial Infarct-Size Limiting Effect of Postconditioning with L-Lactate in Young and Old Rats under Atropine-Induced Blockade of M-Cholinoreceptors

Висмонт

Чепелев

Goubkin

2022

J Evol Biochem Phys

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Comparative evaluation of infarct-limiting efficiency of postconditioning with lactate in ischemia-reperfusion of the myocardium in young and old rats and rats with transient hypercholesterolemia

Чепелев

Висмонт

Goubkin

2022

Vescì Nac. akad. navuk Belarusì, Ser. med. navuk

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Taking into account the high medical and social significance of the problem of treating patients with coronary heart disease and acute myocardial infarction, the search for new effective methods of preventing or weakening ischemic and reperfusion myocardial damage and finding out the mechanisms of their implementation is an urgent task of modern experimental and clinical medicine. The aim of the study was to conduct a comparative analysis and clarification of features of the cardioprotective efficiency of postconditioning with lactate in ischemia-reperfusion of the myocardium in young and old rats and rats with transient hypercholesterolemia (HCE). It was found that remote ischemic postconditioning (RIPostC) in ischemia-reperfusion of the myocardium has an infarction-limiting effect and is accompanied by an increase in the level of lactate in the blood, and lactate after injection into the bloodstream of animals at a dose of 10 mg/kg 25 min after the start of reperfusion leads to a decrease in the size of the necrosis zone in the left ventricular myocardium in young and old rats. However, postconditioning with lactate is not effective in limiting the size of the zone of necrosis in the left ventricular of myocardium in young and old rats with transient HCE. There is reason to suppose that hyperlactatemia takes part in the realization of the cardioprotective effect of RIPostC. The presence of such a risk factor for cardiovascular diseases as HCE can serve as a criterion for excluding the use of postconditioning with lactate as a way to reduce ischemic and reperfusion damage to the myocardium in patients with acute myocardial infarction.

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Cardioprotective efficiency of pharmacological postconditioning using lactic acid in ischemia-reperfusion of the myocardium in rats with transitional hypercholesterolemia

Cited by 4 publications

References 23 publications

Participation of L-lactate in the cardioprotective effect of remote ischemic postconditioning in young and old rats

Participation of L-lactate in the cardioprotective effect of remote ischemic postconditioning in young and old rats

Myocardial Infarct-Size Limiting Effect of Postconditioning with L-Lactate in Young and Old Rats under Atropine-Induced Blockade of M-Cholinoreceptors

Comparative evaluation of infarct-limiting efficiency of postconditioning with lactate in ischemia-reperfusion of the myocardium in young and old rats and rats with transient hypercholesterolemia

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