Abstract
Introduction. The pathophysiological mechanisms of cardiac injury in Takotsubo syndrome are currently poorly understood. The role of adrenergic receptor (AR) subtypes in the development of stress-induced myocardial injury (SIMI) remains unclear.Aim. To assess the role of β-ARs in the development of SIMI.Material and Methods. The study was performed using female Wistar rats (n = 84). Rats were subject to 24-hour immobilization in the supine position to simulate SIMI. 99mTc-pyrophosphate radiopharmaceutical was used to determine the degree of cardiac injury.Results. The study showed that β-AR blockade with propranolol reduced the degree of cardiac injury by 38.4%. Selective β1- AR antagonists, atenolol and nebivolol, led to 2.00- and 2.55-fold decreases in 99mTc pyrophosphate accumulation in the heart, respectively. Blockade of β2-ARs by a selective antagonist ICI-118.551 caused an increase in the degree of 99mTc-pyrophosphate accumulation in the heart by 34.6%. A selective β3-AR antagonist L-748337 did not affect 99mTc pyrophosphate accumulation in the heart.Conclusions. The study showed that β1-ARs are involved in the damaging effects of stress on the heart during immobilization stress. β2-AR had a cardioprotective effect in immobilization. β3-AP did not play a significant role in the stress-induced cardiac injury with a single exposure to the stressor.
Highlights
The pathophysiological mechanisms of cardiac injury in Takotsubo syndrome are currently poorly understood
The study showed that β-adrenergic receptor (AR) blockade with propranolol reduced the degree of cardiac injury by 38.4%
(Med.), Research Scientist, Laboratory of Experimental Cardiology, Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences
Summary
Исследование было выполнено на 84 крысах-самках линии Вистар. В экспериментальных группах животные подвергались иммобилизационному стрессу, в ходе которого крыс фиксировали в течение 24 ч в положении на спине. Раствор 99mTc-ПФ готовился непосредственно перед применением из элюата технеция (генератор технеция TEKCIS, Франция) и препарата Пирфотех (ООО Диамед, Россия). 99mTc-ПФ вводили внутривенно в дозе 100 МБк/кг через 30 мин после прекращения иммобилизации. Препараты вводили внутрибрюшинно 2 раза: за 30 мин до иммобилизации и через 12 ч после иммобилизации. Препарат ICI 118,551 вводили 3 раза с интервалом 8 ч. Роль β-адренорецепторов в стресс-индуцированном повреждении сердца (-)-пропранолол в дозе 2,5 мг/кг. Селективный антагонист β1-АР атенолол использовали в дозе 1 мг/кг [13], селективный антагонист β1-АР небиволол – в дозе 1,2 мг/кг [14]. Селективный антагонист β3-АР L-748337 вводили в дозе 0,1 мг/кг, антагонист β2-АР ICI 118,551 в дозе 0,3 мг/кг. Для выявления статистически значимых различий использовали H-критерий Краскела – Уоллиса с последующим применением апостериорного критерия Данна
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