STAT5 Activation and Cardioprotection by Remote Ischemic Preconditioning in Humans

Rationale: The heart can be protected from infarction by brief episodes of ischemia/reperfusion of a remote organ. Remote ischemic preconditioning (RIPC) by brief arm ischemia/reperfusion has been recruited in patients undergoing coronary artery bypass surgery or percutaneous coronary interventions and during transport to the hospital for acute myocardial infarction. Cardioprotective signaling has been extensively characterized in animal experiments. Objective: To identify cardioprotective signaling by RIPC in humans. Methods and Results: RIPC was induced by 3 cycles of 5 minutes of arm ischemia/5 minutes of reperfusion in patients undergoing coronary artery bypass surgery. Twelve patients each were randomly assigned to undergo RIPC or a sham control procedure. Protection was confirmed by reduced serum troponin I concentrations in patients with RIPC versus control patients. In myocardial biopsies, an array of established cardioprotective proteins was analyzed by Western immunoblotting. The phosphorylation of signal transducer and activator of transcription 5 (STAT5) increased from baseline before ischemic cardioplegic arrest to 10 minutes of reperfusion with RIPC, and STAT5 phosphorylation during reperfusion was greater in patients with RIPC than in control patients. Conclusions: The identification of this unique signaling signature of RIPC will facilitate the development of pharmacological cardioprotection. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01406678.