Abstract
Aim
Despite an increased rate of return of spontaneous circulation (ROSC) in out-of-hospital
cardiac arrest (OHCA) patients, almost half of patients do not survive up to hospital
discharge. Understanding pathophysiological mechanisms of post-cardiac arrest syndrome
is essential for developing novel therapeutic strategies. During systemic inflammatory
responses and concomitant cell death, double-stranded (ds) DNA is released into circulation,
exerting pro-inflammatory effects. Deoxyribonuclease (DNase) degrades dsDNA. The role
of DNase activity in OHCA survivors and impact on clinical outcome has not been analyzed
yet.
Methods
In a prospective, single-center study, dsDNA and DNase activity were determined at
hospital admission (acute phase) and 24 h (subacute phase) after ROSC. The ratio between
dsDNA levels and DNase activity was calculated to determine the extent of dsDNA release
in relation to the patients’ capacity of degradation. Thirty-day mortality was defined
as study end point.
Results
We enrolled 64 OHCA survivors, of whom 26.6% (n = 17) died within 30 days. A peak of circulating dsDNA was observed at admission
which decreased within 24 h. DNase activity did not differ between acute and subacute
phase, while dsDNA load per DNase activity significantly decreased. The ratio between
dsDNA levels and DNase activity in the subacute phase was the strongest predictor
of 30-day mortality with an adjusted HR per 1 SD of 3.59 (95% CI, 1.80–7.18, p < 0.001).
Conclusion
Disproportionally increased dsDNA levels uncompensated by DNase activity are a strong
predictor of mortality in OHCA survivors. This pilot study points to a potentially
protective effect of DNase activity in patients undergoing cardiac arrest.
Keywords
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Article info
Publication history
Published online: April 03, 2020
Accepted:
March 13,
2020
Received in revised form:
February 24,
2020
Received:
November 7,
2019
Identification
Copyright
© 2020 Elsevier B.V. All rights reserved.