Effects of Remote Ischemic Preconditioning in Patients with Concentric Myocardial Hypertrophy: A Randomized, Controlled Trial with Molecular Insights

Background: Efficacy of remote ischemic preconditioning (RIPC) for cardioprotection in cardiac surgery is controversial. We aimed to evaluate the clinical and molecular effects of RIPC on the concentrically hypertrophied myocardium.

Methods: Seventy-two aortic stenosis patients receiving aortic valve replacement (AVR) under sevoflurane anesthesia were randomly allocated to RIPC (3cycles of 5-min inflation [300mmHg] and deflation on the left arm) or control (deflated cuff placement) group. The primary endpoints were 24-h area under the curve (AUC) for serum creatine kinase (CK)-MB and troponin (Tn)-T levels. The secondary endpoints were myocardial activation of cell signaling pathways, including reperfusion injury salvage kinases (RISK), signal transducer and activator of transcription (STAT), nitric oxide synthase (NOS), and apoptosis related molecules, obtained from right atrial tissue before and after cardiopulmonary bypass (CPB).

Results: There were no intergroup differences in 24-h AUCs of CK-MB and Tn-T. Phosphorylations of RISK pathway molecules were not enhanced by RIPC before and after CPB. Phosphorylation of STAT5 was significantly lower in the RIPC group before and after CPB. Phosphorylations of STAT3 and endothelial NOS were not enhanced by RIPC before and after CPB. Expression level of cleaved caspases-3/caspase-3 was significantly higher in the RIPC group before CPB.

Conclusions: RIPC did not provide clinical benefits or activate protective signaling in patients with concentric left ventricular hypertrophy undergoing AVR.