Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Pediatr Res. 2022 Nov;92(5):1309-1315. doi: 10.1038/s41390-022-01964-6. Epub 2022 Feb 4.
Catecholamine-storm is considered the major cause of enterovirus 71-associated cardiopulmonary death. To elucidate the effect of milrinone on cardiac mitochondria and death, a rat model of catecholamine-induced heart failure was investigated.
Young male Spray-Dawley rats received a continuous intravenous infusion of norepinephrine then followed by co-treatment with and without milrinone or esmolol. Vital signs were monitored and echocardiography was performed at indicated time points. At the end of experiments, hearts were extracted to study mitochondrial function, biogenesis, and DNA copy numbers.
Hypernorepinephrinemia induced persistent tachycardia, hypertension, and high mortality and significantly impaired the activities of the electron transport chain and suppressed mitochondrial DNA copy number, mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-α. Norepinephrine-induced hypertension could be significantly suppressed by milrinone and esmolol. Milrinone improved but esmolol deteriorated the survival rate. The left ventricle was significantly enlarged shortly after norepinephrine infusion but later gradually reduced in size by milrinone. The impairment and suppression of mitochondrial function could be significantly reversed by milrinone but not by esmolol.
Milrinone may protect the heart via maintaining mitochondrial function from hypernorepinephrinemia. This study warrants the importance of milrinone and the preservation of mitochondrial function in the treatment of catecholamine-induced death.
Milrinone may protect the heart from hypernorepinephrinemia-induced death via maintaining myocardial mitochondrial activity, function, and copy number. Maintenance of cardiac mitochondrial function may be a potential therapeutic strategy in such catecholamine-induced heart failure.
儿茶酚胺风暴被认为是肠病毒 71 相关心肺死亡的主要原因。为了阐明米力农对心脏线粒体和死亡的影响，研究了一种儿茶酚胺诱导心力衰竭的大鼠模型。
年轻雄性 Spray-Dawley 大鼠接受持续静脉输注去甲肾上腺素，然后分别用米力农和艾司洛尔联合或不联合治疗。监测生命体征并在指定时间点进行超声心动图检查。实验结束时，提取心脏以研究线粒体功能、生物发生和 DNA 拷贝数。
高去甲肾上腺素血症引起持续心动过速、高血压和高死亡率，并显著损害电子传递链的活性，抑制线粒体 DNA 拷贝数、线粒体转录因子 A 和过氧化物酶体增殖物激活受体-γ共激活因子 1-α。米力农和艾司洛尔可显著抑制去甲肾上腺素诱导的高血压。米力农可改善但艾司洛尔可降低生存率。去甲肾上腺素输注后不久左心室明显增大，但随后逐渐缩小。米力农可显著逆转线粒体功能的损害和抑制，但艾司洛尔不能。
米力农可能通过维持线粒体功能来保护心脏免受高去甲肾上腺素血症的影响。这项研究证明了米力农和保存线粒体功能在治疗儿茶酚胺诱导死亡中的重要性。
米力农可能通过维持心肌线粒体活性、功能和拷贝数来保护心脏免受高去甲肾上腺素血症诱导的死亡。维持心脏线粒体功能可能是治疗此类儿茶酚胺诱导心力衰竭的潜在治疗策略。
