Intestinal Ischemia as a Stimulus for Systemic Inflammatory Response After Cardiac Arrest

Out-of-hospital cardiac arrest (CA) is a leading public health problem causing nearly one
third of a million deaths annually in the US, accounting for half of all cardiovascular
deaths and surpassing deaths from stroke, heart failure, and breast and lung cancer combined.
Twenty to fifty percent of CA patients (pts) can be resuscitated initially but many die
before hospital discharge or suffer permanent neurologic damage. Therapeutic hypothermia (TH)
improves survival and neurological outcomes. Despite aggressive, targeted post arrest
management, including TH, approximately 50% of pts die before leaving the hospital due to
global ischemia-reperfusion injury (IRI) known as the "post arrest syndrome", 1 which is a
sepsis-like state characterized by elevated markers of cellular inflammation and injury. It
is believed that TH works by decreasing the body's basal metabolic rate (BMR) and attenuating
the systemic inflammatory response (SIR). However, specific triggers of the intense
pro-inflammatory response are unclear. This "gap" in knowledge must be closed to identify
targeted therapy to decrease IRI and improve outcomes.

Blood flow to the gut is decreased markedly and intestinal tissue becomes ischemic during CA
and CPR, particularly when vasoconstrictor drugs such as epinephrine, are given. IRI of the
intestine increases intestinal permeability leading to intestinal microbial translocation and
endotoxin release that can stimulate and perpetuate systemic inflammation and cause
subsequent multi-organ dysfunction. Endotoxin also increases body temperature and energy
expenditure and may attenuate TH induced reductions in BMR and hence, decrease efficacy. The
purpose of this novel pilot study is to detect systemic endotoxin release following CA in
humans and determine association with cytokine activation, and BMR alterations during TH.