Pharmacological Neuroprotection in Cardiac Surgery: Effectiveness of Pharmacologic-Preconditioning with Erythromycin

Regardless of the degree of advances in neuroprotective strategies, and despite the technological progress in neuromonitoring, brain injury still remains the “Achilles' heel” in cardiac surgery. A large number of pharmacological and non-pharmacological therapeutic interventions have been investigated during the last two decades. Recently, both theoretical and experimental findings suggest benefits of pharmacological cerebral protection, although, there is no conclusive evidence of clinical superiority of specific agents that have been applied as neuroprotectants, in human randomized controlled trials. Pre-ischemic conditioning has also been used in an attempt to reduce the incidence of brain injury following cardiac surgery. In light of previous evidence showing that pharmacologic preconditioning with a single dose of erythromycin induces tolerance against transient global cerebral ischemia in rats, we examined whether erythromycin would reduce the number of apoptotic neurons in the neocortex in our acute porcine model of hypothermic circulatory arrest (HCA). Pre-ischemic conditioning with a single dose of the antibiotic erythromycin, applied 12 h before HCA, significantly reduced neuronal injury in the neocortex of the porcine brain, suggesting that cerebral protection may be achieved with erythromycin pharmacological preconditioning in cardiac surgery on an experimental basis. Since erythromycin has been effectively used in clinical practice with few side effects, these findings suggest that it could be a promising candidate for potential clinical neuroprotective strategy.