Abstract
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.
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Funding
This work was supported by grant CMRPG8G0571 from Chang Gung Memorial Hospital, Kaohsiung, Taiwan to I.-C.L. and M.-H.L.
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I.-C.L.: conception and design of the study, acquisition, analysis, and interpretation of data, and drafting and revising the manuscript. K.L.H.W.: conception and design of the study, analysis, and interpretation of data, and drafting and revising the manuscript. C.-W.W., Y.-J.L., and M.-H.L.: acquisition, analysis, and interpretation of data, and revising the manuscript. K.-S.H. and J.Y.H.C.: supervision of data acquisition and revising the manuscript. All authors made final approval of the version and agreed to be accountable for all aspects of the work.
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Lin, IC., Wu, CW., Lin, YJ. et al. Milrinone effects on cardiac mitochondria, hemodynamics, and death in catecholamine-infused rats. Pediatr Res 92, 1309–1315 (2022). https://doi.org/10.1038/s41390-022-01964-6
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DOI: https://doi.org/10.1038/s41390-022-01964-6
