Abstract
Sudden cardiac arrest (CA) is associated with high mortality and morbidity rates, largely due to detrimental effects of global ischemia on every organ. Notably, clinical evidence indicates that gastrointestinal tract damage is frequently observed in successfully resuscitated CA patients and suggests that this damage has a negative impact on prognosis. However, experimental CA studies have rarely examined this clinically relevant pathologic change and as such, little is known about the underlying mechanisms. Here, we provide the first evidence that mast cells (MCs) play a critical role in gut damage after CA. Our data first showed notable activation of intestinal MCs and evidence of disrupted gut integrity following CA in a mouse model. Then, using both pharmacologic and genetic tools, we found that treatment with the MC activator C48/80 significantly increased gut permeability, while gut function was better preserved in MC-deficient mice compared to wild-type mice. Together, our results identified MC activation as a critical pathologic process driving post-CA gut damage.