Coenzyme Q10 in Post-Cardiac Arrest Cerebral Resuscitation

Cardiac arrest (CA) occurs in nearly 350,000 patients in the U.S. each year with an
estimated mortality of 60% in those surviving the initial arrest. Moreover, the overall
prognosis for survivors is often limited by neurologic injury. Two randomized control trials
(RCTs) have demonstrated that therapeutic hypothermia (TH) after CA improves survival and
reduces neurologic morbidity. As a result of these studies, TH has become the standard of
care in post-CA patients. The mechanism of action for TH is hypothesized to be a reduction
in cerebral oxygen consumption that occurs following an ischemia-reperfusion injury. Another
similar potential target following ischemia-reperfusion injury is mitochondrial function in
the injured brain cells and attenuation of potentially damaging oxygen-free radicals.
Specifically, optimizing mitochondrial function and reducing oxygen free radicals may
enhance cellular function and mitigate cellular injury thereby leading to improved
neurologic outcomes. Coenzyme Q10 (CoQ10) is an essential mitochondrial co-factor and free
radical scavenger that has been found to have neuroprotective effects in various
neurodegenerative disorders such as Parkinson's disease and Huntington's disease. Whether
CoQ10 can provide neuroprotection in acute ischemia-reperfusion injury remains less clear,
but has been recognized by the American Heart Association as a potentially promising
neuroprotective agent. We hypothesize that the administration of exogenous CoQ10 will raise
serum concentrations of CoQ10 and as such may mitigate the adverse effects of the post-CA
ischemia-reperfusion injury on the brain by optimizing mitochondrial function and reducing
oxygen-free radicals. We support this hypothesis by the following:

1. Ischemia-reperfusion injury disrupts normal mitochondrial function and increases O2
free radicals.

2. CoQ10 has been found to attenuate the effects of ischemia-reperfusion injury through
optimizing mitochondrial function and mitigation of cellular apoptosis.

3. CoQ10 has neuroprotective effects in other neurodegenerative disorders.

4. Our group has unpublished preliminary data showing low CoQ10 levels in a majority of
patients with septic shock, and that lower CoQ10 levels are significantly associated
with multiple markers of the inflammatory cascade.

5. A pilot human trial in post-CA patients demonstrated a reduction in mortality and trend
toward reduction in neurologic morbidity.

To test our hypothesis, we propose the following pilot study as proof of concept in
preparation for a larger multicenter trial powered toward neurologic outcome and mortality.
This pilot study will allow for a more informed power analysis for a larger trial, provide
proof of concept for enrollment and administration of therapy, examine the time-frame for
drug absorption into serum, and evaluate for tolerability.

Inclusion Criteria:

1. Adult patients (age > 18 years)

2. Comatose after CA with subsequent return of spontaneous circulation

Exclusion Criteria:

1. Comatose status prior to CA

2. CoQ10 therapy within one month prior to CA

3. Pregnancy