Development and evaluation of a novel mouse model of asphyxial cardiac arrest revealed severely impaired lymphopoiesis after resuscitation

Wei Wang, Ran Li, Wanying Miao, Cody Evans, Liping Lu, Jingjun Lyu, Xuan Li, David S. Warner, Xiaoping Zhong, Ulrike Hoffmann, Huaxin Sheng, Wei Yang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

BACKGROUND: Animal disease models represent the cornerstone in basic cardiac arrest (CA) research. However, current experimental models of CA and resuscitation in mice are limited. In this study, we aimed to develop a mouse model of asphyxial CA followed by cardiopulmonary resuscitation (CPR), and to characterize the immune response after asphyxial CA/CPR. METHODS AND RESULTS: CA was induced in mice by switching from an O2 /N2 mixture to 100% N2 gas for mechanical ventilation under anesthesia. Real-time measurements of blood pressure, brain tissue oxygen, cerebral blood flow, and ECG confirmed asphyxia and ensuing CA. After a defined CA period, mice were resuscitated with intravenous epinephrine administration and chest compression. We subjected young adult and aged mice to this model, and found that after CA/CPR, mice from both groups exhibited significant neurologic deficits compared with sham mice. Analysis of post-CA brain confirmed neuroinflammation. Detailed characterization of the post-CA immune response in the peripheral organs of both young adult and aged mice revealed that at the subacute phase following asphyxial CA/CPR, the immune system was markedly suppressed as manifested by drastic atrophy of the spleen and thymus, and profound lymphopenia. Finally, our data showed that post-CA systemic lymphopenia was accompanied with impaired T and B lymphopoiesis in the thymus and bone marrow, respectively. CONCLUSIONS: In this study, we established a novel validated asphyxial CA model in mice. Using this new model, we further demonstrated that asphyxial CA/CPR markedly affects both the nervous and immune systems, and notably impairs lymphopoiesis of T and B cells.

Original languageEnglish (US)
Article numbere019142
JournalJournal of the American Heart Association
Volume10
Issue number11
DOIs
StatePublished - 2021
Externally publishedYes

Keywords

  • Asphyxia
  • Cardiac arrest
  • Immunology
  • Immunosuppression
  • Lymphocyte
  • Lymphopenia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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