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Milrinone effects on cardiac mitochondria, hemodynamics, and death in catecholamine-infused rats
I-Chun Lin1, Chih-Wei Wu2, Ying-Jui Lin3
1Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. mslinichun@gmail.com.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Impact:
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.
Insights
Milrinone protects the heart from catecholamine-induced death by preserving mitochondrial function. This study highlights milrinone
Area of Science:
- Cardiovascular Research
- Mitochondrial Biology
- Pharmacology
Background:
- Catecholamine-storm is a primary cause of enterovirus 71-associated cardiopulmonary death.
- Understanding milrinone's effect on cardiac mitochondria is crucial for treating heart failure.
Purpose of the Study:
- To investigate the impact of milrinone on cardiac mitochondria and mortality in a rat model of catecholamine-induced heart failure.
- To evaluate milrinone's efficacy in counteracting norepinephrine-induced cardiovascular and mitochondrial dysfunction.
Main Methods:
- Rats received norepinephrine infusion, followed by co-treatment with milrinone or esmolol.
- Vital signs, echocardiography, and cardiac mitochondrial function (including DNA copy number and key factors) were assessed.
Main Results:
- Norepinephrine caused tachycardia, hypertension, high mortality, and impaired mitochondrial function.
- Milrinone improved survival rates and reversed mitochondrial damage, unlike esmolol.
- Milrinone mitigated left ventricular enlargement induced by norepinephrine.
Conclusions:
- Milrinone demonstrates cardioprotective effects by maintaining myocardial mitochondrial activity and function during hypernorepinephrinemia.
- Preserving cardiac mitochondrial function emerges as a potential therapeutic strategy for catecholamine-induced heart failure.
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