P2284Impact of remote ischemic preconditioning in cardiosurgical patients on contractile and mitochondrial function of right atrial tissue

Abstract

Introduction: Remote ischemic preconditioning (RIPC) by 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. Purpose: We aimed to identify a functional parameter reflecting the RIPCinduced protection in humans. We measured a) the contractile function of isolated right atrial trabeculae before and during hypoxia/reoxygenation, and b) mitochondrial function in right atrial tissue, both obtained from patients undergoing coronary artery bypass grafting (CABG) with RIPC or placebo, respectively. Methods: Patients undergoing elective CABG surgery under isoflurane/sufentanil anaesthesia, cardiopulmonary bypass and ischemic cardioplegic arrest were randomized to RIPC by 3 cycles of 5 min blood pressure cuff inflation on the left upper arm /5 min deflation or placebo (cuff left uninflated) before skin incision. Right atrial appendages from 94 patients were harvested prior to cardioplegic arrest (RIPC: n=45, placebo: n=49). Myocardial protection by RIPC was assessed from serum troponin I/T concentrations over 72 h after surgery. Trabeculae (RIPC: n=35, placebo: n=39) were isolated in cardioplegic buffer and transferred to Tyrode buffer. Electrically initiated developed force of contraction (mN) was measured. After baseline measurements, hypoxia/reoxygenation (60 min/30 min) was induced by changing the buffer gas and electrical stimulation frequency (1 to 3 Hz). Mitochondria were isolated (RIPC: n=10, placebo: n=10), and respiration, adenosine triphosphate (ATP) production, reactive oxygen species (ROS) production and calcium retention capacity (CRC) to estimate mitochondrial permeability transition pore (mPTP) opening were measured at 37°C. Results: Associated with the observed cardioprotection (13% decrease in the area under the curve of troponin I/T with RIPC vs. placebo), baseline contractile function and recovery of contractile function during reoxygenation were improved (Fig. 1A). Basal respiration was not different, but adenosine diphosphate (ADP)‐ stimulated complex I respiration was greater with RIPC than with placebo. Mitochondrial ascorbate/tetramethyl‐p‐phenylenediamine (TMPD)‐stimulated complex IV respiration and maximal oxygen uptake of uncoupled mitochondria were not different between RIPC and placebo, reflecting an equal loading of viable mitochondria (Fig. 1B). Mitochondrial ATP production (Fig. 1C) was greater whereas mitochondrial ROS production (Fig 1D) was less with RIPC vs. placebo. Mitochondrial CRC (Fig 1E) was improved with RIPC vs. placebo, with and without cyclosporine A. Conclusion: RIPC by repetitive upper arm ischemia/reperfusion reduces troponin release and improves ex vivo contractile function of human right atrial trabeculae before and after hypoxia/reoxygenation. Improved contractile function goes along with improved mitochondrial function. (Figure Presented).