Improvement of mitochondrial function in human atrial tissue by remote ischemic conditioning

Abstract

IntroductionRemote ischemic preconditioning (RIPC), repeated cycles of brief limb ischemia/reperfusion, attenuates postoperative troponin release in patients undergoing surgical coronary revascularization and improves clinical outcome in some, but not all studies. Mitochondria are the end‐effectors of cardioprotection by local ischemic conditioning maneuvers in experimental studies. Here, we now analyzed mitochondrial function in response to RIPC in human atrial tissue.MethodsPatients undergoing elective surgical coronary revascularization under isoflurane anesthesia were randomized to RIPC by 3× 5 min/5 min upper arm blood pressure cuff inflation/deflation or placebo (n=30/30), and their right atrial appendages were harvested prior to ischemic cardioplegic arrest. Cardioprotection was reflected by a 14% decrease with RIPC vs. placebo in the area under the curve of serum troponin I/T concentrations over 72 h after surgery. Mitochondria were isolated from the atrial tissue (n=10/10). Mitochondrial function, i.e. mitochondrial respiration, adenosine triphosphate (ATP) production, reactive oxygen species (ROS) production and calcium retention capacity (CRC) to estimate mitochondrial permeability transition pore (mPTP) opening, was measured at physiological temperature of 37°C. Data are given as mean±SEM.ResultsAssociated with the observed cardioprotection in patients, mitochondrial function was improved by RIPC. Basal respiration was not different between RIPC and placebo. ADP‐stimulated complex I respiration was significantly greater with RIPC than with placebo. Mitochondrial complex IV respiration and maximal oxygen uptake of uncoupled mitochondria were not different between RIPC and placebo, reflecting an equal loading of viable mitochondria (Figure 1A). The mitochondrial ATP production (Figure 1B) was greater whereas mitochondrial ROS production (Figure 1C) was less with RIPC than with placebo. CRC of mitochondria (Figure 1D) was improved with RIPC in comparison to placebo, with and without cyclosporine A.ConclusionIn human myocardium, mitochondria are an intracellular target of protection by RIPC.Support or Funding InformationSupported by: German Research Foundation (SFB 1116 B8)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.