Potential humoral mediators of remote ischemic preconditioning in patients undergoing surgical coronary revascularization

Remote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion may reducemyocardial ischemia/reperfusion injury and improve patients prognosis after elective coronary artery bypass graft (CABG) surgery. The signal transducer and activator of transcription (STAT) 5 activation in left ventricular myocardium is associated with RIPC's cardioprotection. Cytokines and growth hormones typically activate STATs and could therefore act as humoral transfer factors of RIPC's cardioprotection. We here determined arterial plasma concentrations of 25 different cytokines, growth hormones, and other factors which have previously been associated with cardioprotection, before (baseline)/after RIPC or placebo (n = 23/23), respectively, and before/after ischemic cardioplegic arrest in CABG patients. RIPC induced protection was reflected by a 35% reduction of serum troponin I release. With the exception of interleukin-1 alpha, none of the humoral factors changed in their concentrations after RIPC or placebo, respectively. Interleukin-1 alpha, when normalized to baseline, increased after RIPC (280 +/- 56%) but not with placebo (97 +/- 15%). The interleukin-1 alpha concentration remained increased until after ischemic cardioplegic arrest and was also higher than with placebo in absolute concentrations (25 +/- 6 versus 16 +/- 3 pg/mL). Only interleukin-1 alpha possibly fulfills the criteria which would be expected from a substance to be released in response to RIPC and to protect the myocardium during ischemic cardioplegic arrest.