The quest for the “Holy Grail” of ischemic stroke cytoprotection

Coronary artery bypass grafting (CABG) has been performed for over 40 years. Operative techniques have evolved, and CABG can now be done either with or without cardiopulmonary bypass, the latter being associated with lower 1-year rates of death, myocardial infarction, and stroke in at least some series.¹ Despite surgical refinements, post-CABG stroke, encephalopathy, and cognitive decline remain important clinical problems.²

Prospective studies demonstrate post-CABG stroke rates up to 5.2% with encephalopathy occurring in 14%.² The pathophysiologic bases of these neurologic complications may in part be related to microemboli, hypoperfusion, and postoperative atrial fibrillation. Independent risk factors for neurologic perioperative events are similar to those for systemic vascular disease (e.g., hypertension, diabetes, peripheral vascular disease, prior stroke, and age).² Although predictive models can be helpful in identifying CABG patients at untoward neurologic risk, drugs to protect the brain would have the potential to decrease the consequences of ischemic injury.

Achieving the goal of identifying a clinically effective cytoprotective drug that could positively and meaningfully affect patient outcomes when given after ischemic stroke has been elusive. Of the numerous compounds having such properties in laboratory experiments, none has proven beneficial in clinical trials.³ There are …