International journal of cardiology · 2025
Increased sympathetic outflow induced by ventromedial hypothalamic nucleus activation aggravates cardiac electrophysiology disturbance after myocardial ischemia-reperfusion injury.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Xu Xiao, Liu Zihan, Liu Zhihao, Li Zeyan, Zhou Yuyang, Zhou Huixin, Tan Wuping, Peng Chen, Cheng Siyi, Wang Yueyi, Zhou Liping, Zhou Xiaoya, Jiang Hong
Аннотация
BACKGROUND AND AIMS: The ventromedial hypothalamus (VMH) is the key brain region related to emotional stress and sympathetic activity, which can exacerbate myocardial ischemia-reperfusion (I/R) injury and induce severe ventricular arrhythmia (VA). We aim to investigate the role of increased sympathetic outflow induced by VMH activation after myocardial I/R injury, especially the changes of cardiac electrical activity.
METHODS: Sprague-Dawley rats were divided randomly into the Sham, I/R, hM3d(Gq) and hM4d(Gi) groups, with VMH specifically activated or inhibited using Designer Receptors Exclusively Activated Designer Drugs (DREADDs) technology. I/R model was inducted by ligation of the left coronary artery for 45 min. After 24 h of reperfusion, electrocardiogram and cardiac electrophysiological studies were conducted. Then the samples were collected for histopathological and molecular analyses.
RESULTS: VMH was chemogenetically manipulated using DREADDs. The activation of VMH significantly increased systemic and local cardiac sympathetic activity, aggravating I/R injury, which reduced following VMH inhibition. The ventricular electrophysiology disturbance exacerbated following VMH activation and ameliorated following VMH inhibition. The expression of myocardial potassium channel including the rapid delayed rectifier potassium channel (Kcnd3), the inward rectifier potassium channel (Kcnj2) and the slow delayed rectifier potassium channel (Kcnq1) was markedly suppressed following VMH activation, which may represent a key mechanism underlying repolarization abnormalities and increased VA susceptibility.
CONCLUSIONS: VMH activation exacerbated cardiac electrophysiology disturbance and increased the susceptibility of VA after I/R injury via increased sympathetic outflow, a process closely linked to repolarization impairment caused by potassium channel dysfunction.
METHODS: Sprague-Dawley rats were divided randomly into the Sham, I/R, hM3d(Gq) and hM4d(Gi) groups, with VMH specifically activated or inhibited using Designer Receptors Exclusively Activated Designer Drugs (DREADDs) technology. I/R model was inducted by ligation of the left coronary artery for 45 min. After 24 h of reperfusion, electrocardiogram and cardiac electrophysiological studies were conducted. Then the samples were collected for histopathological and molecular analyses.
RESULTS: VMH was chemogenetically manipulated using DREADDs. The activation of VMH significantly increased systemic and local cardiac sympathetic activity, aggravating I/R injury, which reduced following VMH inhibition. The ventricular electrophysiology disturbance exacerbated following VMH activation and ameliorated following VMH inhibition. The expression of myocardial potassium channel including the rapid delayed rectifier potassium channel (Kcnd3), the inward rectifier potassium channel (Kcnj2) and the slow delayed rectifier potassium channel (Kcnq1) was markedly suppressed following VMH activation, which may represent a key mechanism underlying repolarization abnormalities and increased VA susceptibility.
CONCLUSIONS: VMH activation exacerbated cardiac electrophysiology disturbance and increased the susceptibility of VA after I/R injury via increased sympathetic outflow, a process closely linked to repolarization impairment caused by potassium channel dysfunction.