What is Wrong With Cardiac Conditioning? We May be Shooting at Moving Targets

Early recanalization of the occluded culprit coronary artery clearly reduces infarct size in both animal models and patients and improves clinical outcomes. Unfortunately, reperfusion can seldom be accomplished before some myocardium infarcts. As a result there has been an intensive search for interventions that will make the heart resistant to infarction so that reperfusion could salvage more myocardium. A number of interventions have been identified in animal models, foremost being ischemic preconditioning. It protects by activating signaling pathways that prevent lethal permeability transition pores from forming in the heart’s mitochondria at reperfusion. Such conditioning can be accomplished in a clinically relevant manner either by staccato reperfusion (ischemic postconditioning) or by pharmacological activation of the conditioning signaling pathways prior to reperfusion. Unfortunately, clinical trials of ischemic postconditioning and pharmacologic conditioning have been largely disappointing. We suggest that this may be caused by inappropriate use as models intended to mimic the clinical scenario of young healthy animals that receive none of the many drugs currently given to our patients. Patients may be resistant to some forms of conditioning because of comorbidities, for example, diabetes, or they may already be conditioned by adjunct medications, for example, P2Y12 inhibitors or opioids. Incremental technological improvements in patient care may render some app...
Source: Journal of Cardiovascular Pharmacology and Therapeutics - Category: Cardiology Authors: Tags: Review Articles Source Type: research