Cyclooxygenase inhibition prior to ventricular fibrillation induced ischemia reperfusion injury impairs survival and outcomes.

Nonsteroidal anti-inflammatory medications (NSAIDs) are one of the most commonly used analgesics in the world. NSAIDs decrease prostaglandin synthesis through cyclooxygenase inhibition (COX-1 or COX-2). The effects of NSAIDs on survival and outcomes from global ischemia reperfusion events and specifically from cardiac arrest (CA) remain controversial. We hypothesized that NSAIDs prior to global whole-body ischemia reperfusion (I/R) injury impairs survival and outcomes. We explored this hypothesis in our swine model of Cardiac Arrest (CA) which involves global I/R with pretreatment using a predominantly COX-1 inhibitor (Indomethacin [COX-1/min COX-2 Inh], a COX-2 Inhibitor [COX-2-Inh, (Celecoxib)] or placebo control. We determined the effects of each inhibitor on a) survival, b) myocardial injury biomarker (Troponin 1), and c) Autonomic Nervous System (ANS) injury marker (heart rate variability [HRV]) up to 3 h after resuscitation. There were no survivals in COX-1/min COX-2-Inh pretreated animals and, 87% survived in both COX-2 Inhibited and control animals. COX-2 Inh pretreated animals had an 1800 fold increase of Troponin 1 compared to baseline whereas control animals had a 90 fold increase (p < 0.001). These results along with literature review of focal I/R in animal models with COX-2 overexpression, human studies of CA, and post myocardial infarction treatment with NSAIDs, support the hypothesis that NSAIDs prior to an I/R event impairs survival and outcomes. Specifically, predominantly COX-1 inhibition impairs survival, and COX-2 inhibition induces myocardial damage, autonomic nervous system dysfunction, and increases the risk for all-cause mortality and morbidity in humans post-MI which has significant implications for the nearly 10% of the population who are taking NSAIDs.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)