Ischemic Preconditioning in the Intensive Care Unit

Preconditioning is the premise that controlled preemptive exposure to sub-lethal doses of a stressor and can condition an organism or organ to later withstand a lethal dose. This process relies on marshaling endogenous survival resources that have evolved as part of an organism's evolutionary struggle to overcome at times harsh environmental conditions. This preconditioning response occurs through activation of myriad complex mechanisms that run the gamut from alterations in gene expression to the de novo synthesis and post-translational modification of proteins, and it may occur across exposure to a wide variety of stressors (i.e., ischemia, hypoxia, hypothermia, drugs). This review will focus on preconditioning in relation to an ischemic stressor (ischemic preconditioning) and how this process may be harnessed as a protective method to ameliorate targeted acute neurologic diseases especially. There has been considerable eagerness to translate ischemic preconditioning to the bedside, and to that end there have been recent trials examining its efficacy in various clinical settings. However, some of these trials have reached diverging conclusions with a protective effect seen in studies targeting acute kidney injury solely while no benefit was seen in larger trials targeting combined endpoints including cardio-, neuro-, and renoprotection in a cohort of patients undergoing cardiac surgery. While an extensive body of pre-clinical research offers ischemic preconditioning as a robust and highly faithful protective phenomenon, its clinical utility remains unproven. This current state may be due to persisting gaps in our understanding of how best to harness its power. This review will provide an overview of the biological mechanisms proposed to underlie ischemic preconditioning, explore initial disease targets, examine the challenges we must overcome to optimally engage this system, and report findings of recent clinical trials.