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Comparison of Heart Failure in Children with Enterovirus 71 Rhombencephalitis and Cats with Norepinephrine Cardiotoxicity

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Abstract

The mechanism of heart failure in patients with enterovirus 71 rhombencephalitis (brain stem encephalitis) remains unknown. Our previous reports hypothesized that a catecholamine storm induced by rhombencephalitis may account for the heart failure. The aim of this study was to develop a novel feline model of norepinephrine cardiotoxicity and compare the resulting heart failure to that in children with enterovirus 71 rhombencephalitis. Nine of 75 children (12%) with enterovirus 71 rhombencephalitis (5 boys and 4 girls; age, 4–28 months; median age, 16 months) were complicated with left ventricular hypokinesia (ejection fraction, 31 ± 9%). Six cats (weight, 3.03 ± 0.64 kg) were administered intravenous norepinephrine 30 μg/kg/min for 3 hours. Echocardiography assessed the left ventricular diameter and function before and after the administration of norepinephrine. Pathology studies included hematoxylin and eosin stain and in situ terminal deoxyribonucleotidyl transferase-mediated dUTP nick end-labeling assay. In the feline model, norepinephrine induced significant left ventricular dilatation (end diastolic diameter from 1.18 ± 0.19 to 1.62 ± 0.22 cm, p = 0.001; endsystolic diameter from 0.54 ± 0.09 to 1.36 ± 0.32 cm, p = < 0.001) and hypokinesia (ejection fraction from 87.5 ± 4.1 to 35.2 ± 16.3%, p = 0.001). Heart specimens from 4 patients and six cats showed similar pathology findings, including myocardial hemorrhage, cardiomyocyte apoptosis, and coagulative myocytolysis, which is characterized by sarcoplasmic coagulation, granulation, vacuolization, myofibrillar waving, and disruption. Both groups showed no significant inflammatory reaction. In conclusion, heart failure in patients with enterovirus 71 rhombencephalitis is similar to that in cats with norepinephrine cardiotoxicity. Norepinephrine cardiotoxicity may play a role in the pathogenesis of heart failure in enterovirus 71 rhombencephalitis.

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Acknowledgments

We thank professor Si-Kwang Liu from the Animal Medical Center, Caspary Research Institute for Veterinary Research, New York, and professor Shuu-Jiun Wang from National Yang-Ming University, Taipei, Taiwan, for their valuable suggestions. This work was supported by grant TCVGH-927309C from Taichung Veterans General Hospital.

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Authors and Affiliations

  1. Department of Pediatrics, Taichung Veterans General Hospital, Taichung, 407, Taiwan, Republic of China

    Y.-C. Fu, C.-S. Chi & S.-L. Jan

  2. Department of Pediatrics, National Yang-Ming University, Taipei, 112, Taiwan, Republic of China

    Y.-C. Fu, C.-S. Chi & Y.-T. Chen

  3. Department of Education and Research, Taichung Veterans General Hospital, 160, Section 3, Chung-Kang Road, Taichung, 407, Taiwan, Republic of China

    N.-N. Lin, C.-C. Cheng, S.-L. Hsu & Y.-T. Chiu

  4. Department of Pediatrics, Taipei Veterans General Hospital, Taipei, 112, Taiwan, Republic of China

    B. Hwang

  5. Department of Physiology, School of Medicine, China Medical College 404, Taichung, Taiwan, Republic of China

    C.-L. Gong

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  1. Y.-C. Fu
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  2. C.-S. Chi
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  7. S.-L. Hsu
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  9. Y.-T. Chen
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  10. Y.-T. Chiu
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Correspondence to Y.-T. Chiu.

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Fu, YC., Chi, CS., Lin, NN. et al. Comparison of Heart Failure in Children with Enterovirus 71 Rhombencephalitis and Cats with Norepinephrine Cardiotoxicity. Pediatr Cardiol 27, 577–584 (2006). https://doi.org/10.1007/s00246-005-0915-6

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  • DOI: https://doi.org/10.1007/s00246-005-0915-6

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