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.