Proteasome inhibition 1 h following ischemia protects GRK2 and prevents malignant ventricular tachyarrhythmias and SCD in a model of myocardial infarction

摘要

We have reported a marked decrease in total G protein-coupled receptor kinase-2 (GRK2) activity in whole slices of canine EBZ tissue obtained during the subacute 6-24 h period after infarction, resulting in a loss of the ability of the EBZ tissue to become desensitized to p-adrenergic stimulation (23, 24). Subsequent studies demonstrated that pretreatment of the dog by either of two agents, a proteasome inhibitor (22) or a TNF-a sequestrant (23), protected against the loss of GRK2 expression and significantly diminished the ventricular ectopic activity. Although no deaths from SCD occurred in the two treated groups compared with the control animals, the relatively small n for each prevented the reduction in SCD from reaching significance in the separate studies.