Comparison of heart failure in children with enterovirus 71 rhombencephalitis and cats with norepinephrine cardiotoxicity.

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 microg/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.